Apparatus for aspirating, irrigating and cleansing wounds

ABSTRACT

An apparatus for cleansing wounds in which irrigant fluid from a reservoir connected to a conformable wound dressing and wound exudate from the dressing are recirculated by a device for moving fluid through a flow path which passes through the dressing and a means for fluid cleansing and back to the dressing. The cleansing means (which may be a single-phase, e.g. microfiltration, system or a two-phase, e.g. dialytic system) removes materials deleterious to wound healing, and the cleansed fluid, still containing materials that are beneficial in promoting wound healing, is returned to the wound bed. The dressing and a method of treatment using the apparatus.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. application Ser. No.15/647,111, filed on Jul. 11, 2017, which is a continuation of U.S.application Ser. No. 14/585,786, filed on Dec. 30, 2014, which is acontinuation of U.S. application Ser. No. 14/584,274, filed on Dec. 29,2014, which is a continuation of U.S. application Ser. No. 14/485,633,filed on Sep. 12, 2014, which is a continuation of U.S. application Ser.No. 13/363,320, filed Jan. 31, 2012, and issued as U.S. Pat. No.8,834,451, which is a divisional of U.S. application Ser. No.12/416,829, filed Apr. 1, 2009 and issued as U.S. Pat. No. 8,398,614,which is a continuation of U.S. application Ser. No. 10/533,275, filedNov. 9, 2005 and issued as U.S. Pat. No. 7,524,315, which is thenational stage application of PCT/GB03/04647, filed Oct. 28, 2003, whichclaims priority to GB 0224986.0, filed Oct. 28, 2002. The disclosure ofeach of these prior applications is incorporated by reference in itsentirety and should be considered a part of this specification.

BACKGROUND OF THE INVENTION Field of the Invention

The present invention relates to apparatus and a medical wound dressingfor aspirating, irrigating and/or cleansing wounds, and a method oftreating wounds using such apparatus for aspirating, irrigating and/orcleansing wounds. It relates in particular to such an apparatus, wounddressing and method that can be easily applied to a wide variety of, butin particular chronic, wounds, to cleanse them of materials that aredeleterious to wound healing, whilst retaining materials that arebeneficial in some therapeutic aspect, in particular to wound healing.

Description of the Related Art

Before the present invention, aspirating and/or irrigating apparatustherefor were known, and tended to be used to remove wound exudateduring wound therapy. In known forms of such wound therapy, the offtakefrom the wound, especially when in a highly exuding state, is voided towaste, e.g. to a collection bag, as illustrated in DE-A-4 012 232.

Materials deleterious to wound healing are removed in this way.

However, materials that are beneficial in promoting wound healing, suchas growth factors, cell matrix components, and other physiologicallyactive components of the exudate from a wound are lost to the site wherethey can be potentially of most benefit, i.e. the wound bed, when suchtherapy is applied.

Such known forms of wound dressing and aspiration and/or irrigationtherapy systems often create a wound environment under the dressing thatthus may result in the loss of optimum performance of the body's owntissue healing processes, and slow healing and/or in weak new tissuegrowth that does not have a strong three-dimensional structure adheringwell to and growing from the wound bed. This is a significantdisadvantage, in particular in chronic wounds.

It thus would be desirable to provide a system of therapy which canremove materials deleterious to wound healing from wound exudate, whilstretaining materials that are beneficial in promoting wound healing incontact with the wound bed.

Dialysis is a known method of treating bodily fluids such as blood exvivo, to cleanse them of materials that are deleterious to the bodysystemically. Removal of such materials by contact with the dialysate isthe prime purpose of dialysis, whilst also retaining materials such asblood, cells and proteins. Other materials that may have an additionalpositive therapeutic action are potentially lost to the system throughthe dialysis membrane, which is also permeable to them. The balance ofsuch materials in the bodily fluid in recirculation may thus be furtherdepleted.

It would be desirable to provide a system of therapy which can removematerials deleterious to wound healing from wound exudate, withoutsubstantially diluting materials that are beneficial in promoting woundhealing in contact with the wound bed, and which can continuously supplyand recirculate such materials to the wound simultaneously.

Dialysis for treating bodily fluids is also a systemic therapy, sincethe treated fluid is returned to within the body. This is in contrast toa topical therapy in which the treated fluid is recycled outside thebody, e.g. to a wound. Most dialysis also requires large amounts ofbodily fluids such as blood, and consequently the relevant devices tendnot to be portable. Even when in a highly exuding state, chronic woundsproduce relatively little fluid to be treated compared with internalbodily systems and relatively little materials that are beneficial insome therapeutic aspect to be retained in the wound and/or itsenvironment.

SUMMARY OF THE INVENTION

It is therefore desirable

-   -   a) to obviate at least some of the abovementioned disadvantages        of known aspiration and/or irrigation therapy systems, and    -   b) to provide a system of therapy which can remove materials        deleterious to wound healing from wound exudate, whilst        retaining materials that are beneficial in promoting wound        healing in contact with the wound bed.

It is also desirable

-   -   a) to obviate at least some of the abovementioned disadvantages        of known dialysis systems, and    -   b) to provide a system of therapy which can remove materials        deleterious to wound healing from wound exudate, whilst        retaining materials that are beneficial in promoting wound        healing in contact with the wound bed,    -   c) without affecting the body systemically.

It is also desirable

-   -   a) to obviate at least some of the abovementioned disadvantages        of known dialysis systems, and    -   b) to provide a system of therapy which can remove materials        deleterious to wound healing from wound exudate, whilst        retaining materials that are beneficial in promoting wound        healing in contact with the wound bed, and    -   c) is portable.

Vascular supply to, and circulation in, tissue underlying andsurrounding the wound is often compromised. It is therefore desirable toprovide a system of therapy that retains and supplies therapeuticallyactive amounts of materials that are beneficial in reversing this effectwhilst removing deleterious materials, thereby promoting wound healing.

Thus, according to a first aspect of the present invention there isprovided an apparatus for aspirating, irrigating and/or cleansingwounds, characterized in that it comprises

-   -   a) a fluid flow path, comprising        -   i) a conformable wound dressing, having            -   a backing layer which is capable of forming a relatively                fluid-tight seal or closure over a wound and            -   at least one inlet pipe for-connection to a fluid supply                tube, which passes through and/or under the wound-facing                face, and            -   and at least one outlet pipe for connection to a fluid                offtake tube, which passes through and/or under the                wound-facing face,            -   the point at which the or each inlet pipe and the or                each outlet pipe passes through and/or under the                wound-facing face forming a relatively fluid-tight seal                or closure over the wound,            -   at least one inlet pipe being connected to a fluid                recirculation tube, and at least one outlet pipe being                connected to a fluid offtake tube: and        -   ii) a means for fluid cleansing having at least one inlet            port connected to a fluid offtake tube and at least one            outlet port connected to a fluid recirculation tube;    -   b) a fluid reservoir connected by a second fluid supply tube to        an integer of the flow path (optionally or as necessary via        means for flow switching between supply and recirculation);    -   c) a device for moving fluid through the wound dressing and        means for fluid cleansing, and optionally or as necessary the        fluid supply tube; and    -   d) optionally means for bleeding the flowpath,        such that fluid may be supplied to fill the flowpath from the        fluid reservoir via the fluid supply tube (optionally or as        necessary via the means for flow switching) and recirculated by        the device through the flow path.

The means for flow switching between supply and recirculation may takeany form that enables the wound simultaneously to be

-   -   a) put into communication with the fluid reservoir but    -   b) closed to the fluid recirculation tube, and    -   c) vice versa.

Thus, if there is only one inlet pipe that passes through and/or underthe wound-facing face of the wound dressing, the fluid reservoir isconnected by the fluid supply tube to the flow path via means for flowswitching as desired the into a fluid recirculation tube or a fluidofftake tube.

In this case, the means for flow switching between supply andrecirculation may be a regulator, such as a T-valve. This is connectedin turn to two parts of a fluid recirculation tube or a fluid offtaketube and the fluid supply tube, such that the desired flow switchingbetween supply and recirculation is achieved.

If there are two or more inlet pipes, these may be connectedrespectively to a fluid supply tube or fluid recirculation tube,respectively having a first regulator and a second regulator, such as avalve or other control device for admitting fluids into the wound.

The desired flow switching between supply and recirculation is achievedby respectively having the first regulator open when the secondregulator is shut, and vice versa.

The means for bleeding the flowpath may be situated in any appropriatepart of the apparatus that is in contact with the irrigant and/or woundexudate, but is usually within the offtake and/or recirculation tubes.However, it is often as far downstream of and away from the reservoirand the fluid supply tube as possible, so that it may be used to primethe whole of the flowpath from the fluid reservoir via the fluid supplytube.

It may be a regulator, such as a valve or other control device, e.g. aT-valve that is turned to switch between bleed and recirculation, forbleeding fluids from the apparatus, e.g. to a waste reservoir, such as acollection bag.

Alternatively, flow switching between supply and recirculation may notbe desired, but rather concomitant bleeding and/or recirculation isdesired. The latter may occur when the volume of irrigant and/or woundexudate in recirculation is increased by continuing addition to it of

-   -   a) wound exudate, and/or    -   b) fluid passing from a cleansing fluid through a selectively        permeable integer, for example in a system such as a dialysis        unit.

The means for bleeding the offtake and/or recirculation tubes may thenbe provided in the form of a regulator, such as a simple valve or othercontrol device for admitting or blocking the passage of irrigant and/orexudate through a bleed line branching from the recirculation path.

The means for fluid cleansing may as desired be a ‘single-phase system.’

In this, the circulating fluid from the wound and the fluid reservoirpasses through a self-contained system in which materials deleterious towound healing are removed and the cleansed fluid, still containingmaterials that are beneficial in promoting wound healing, is returnedvia the recirculation tube to the Wound bed. Such systems are describedin further detail hereinafter in connection with the means for fluidcleansing.

Alternatively, where appropriate it may be provided in the form of atwo-phase system, such as a dialysis unit, or a biphasic liquidextraction unit.

In this, the circulating fluid from the wound and the fluid reservoirpasses through a system in which the fluid recirculates in indirect or(less usually, direct) contact with a second fluid (dialysate) phase,more usually a liquid, in which materials deleterious to wound healingare removed and the cleansed fluid, still containing materials that arebeneficial in promoting wound healing, is returned via the recirculationtube to the wound bed. Such systems are described in further detailhereinafter in connection with the means for fluid cleansing.

In use, typically, the means for flow switching between supply andrecirculation tubes is set to admit fluid into the wound from the fluidreservoir but to close the wound to the fluid recirculation tube.

Then, any means for bleeding the offtake and/or recirculation tubes areis opened and the device for moving fluid through the wound and meansfor fluid cleansing is started.

The capacity of the apparatus flow path and the flow rate of irrigantand/or wound exudate from the wound will largely determine whether it isappropriate to run the device to prime the apparatus throughout thewhole length of the apparatus flow path, i.e. to displace any existingfluid reservoir (often air) from the fluid recirculation path, and forhow long it should be run. Typically, there is a preponderance ofirrigant from the fluid reservoir over wound exudate in recirculation,so that use of the device for moving fluid through the wound isappropriate for this purpose.

It is allowed to run until the apparatus is primed throughout the wholelength of the apparatus flow path.

Then, typically the means for bleeding the offtake and/or recirculationtubes is closed, and the means for flow switching between supply andrecirculation tubes is set to close the wound to the fluid reservoir butto admit fluid into the wound from the fluid recirculation tube.

If the means for fluid cleansing is a two-phase system, such as adialysis unit, or a biphasic extraction unit, the cleansing fluid istypically set in motion in contact with the surface of the selectivelypermeable integer, for example the polymer film, sheet or membrane. Ofcourse, the cleansing fluid may less usually be static, and then thisstep is omitted.

As noted below in more detail, the volume of irrigant and/or woundexudate from the wound in recirculation may be increased by continuingaddition to it of

-   -   a) wound exudate, and/or    -   b) fluid passing from a cleansing fluid through a selectively        permeable integer, for example the polymer film, sheet or        membrane of a two-phase system, such as an dialysis unit.

Additionally or alternatively, it may be desired to apply a negativepressure to the wound by means of a device for moving fluid through thewound and means for fluid cleansing applied to the fluid inrecirculation in the fluid recirculation tube downstream of and awayfrom the wound dressing.

In such case, it may be desirable to provide a system in whichconcomitant bleeding and/or recirculation is possible, and to make thenecessary adjustments to maintain the desired balance of fluid inrecirculation by means of the means for bleeding the offtake and/orrecirculation tubes.

The volume of irrigant and/or wound exudate from the wound inrecirculation may be decreased by continuing loss from it of fluidpassing from a cleansing fluid through a selectively permeable integer,for example in a system such as a dialysis unit.

Additionally or alternatively, it may be desired to apply a positivepressure to the wound by means of a device for moving fluid through thewound and means for fluid cleansing applied to the fluid inrecirculation in the fluid recirculation tube upstream of and towardsthe wound dressing.

The means for flow switching between supply and recirculation may besimilarly provided in a form in which concomitant supply and/orrecirculation is possible, and to make the necessary adjustments tomaintain the desired balance of fluid in recirculation by means of themeans for flow switching.

It will be appreciated that where a positive or negative pressure is tobe applied to the wound, at least one hollow body in the recirculationflow path to and from the wound bed should have sufficient resilienceagainst the pressure to allow any significant compression ordecompression of the irrigant fluid to occur.

In all embodiments of the apparatus, the type and material of suchbodies (which are defined by a film, sheet or membrane) that aredescribed by way of example herein to be suitable for use in the presentinvention will be largely capable of this function.

Thus, examples of suitable materials for bodies defined by a film, sheetor membrane, such as inlet or offtake and/or recirculation tubes andstructures such as bags, chambers and pouches, filled with irrigantfluid, e.g. the backing layer of the wound dressing are suitablyelastically resilient thermoplastic materials that are potentiallycapable of this function when pressure is applied in this way.

The present invention in this aspect provides several advantages.

One is that application of a positive pressure to the wound under thebacking layer may make it possible to flood the tissue underlying thewound with one or more physiologically active components.

This may be effected in therapeutically active amounts, to promotegreater wound healing than by treatment with the fluid physiologicallyactive component(s) alone.

Such physiologically active components of the exudate that arebeneficial to wound healing may be e.g. be enzymes or other species andmay be supplied from the dialysate of a dialytic means for fluidcleansing.

It is believed that using the apparatus for aspirating, irrigatingand/or cleansing wounds of the present invention cyclically the effectsmay be further enhanced.

Circulating wound fluid aids in movement of biological signallingmolecules involved in wound healing to locations in the wound bed thatare favourable to the wound healing process and/or to cells that wouldotherwise not be exposed to them, e.g. in a highly exuding wound.

This is especially the case in those embodiments of the apparatus ofthis first aspect of the present invention for aspirating, irrigatingand/or cleansing wounds where there is an inlet or outlet manifold fromwhich tubules radiate and run to the wound bed to end in openings thatdeliver and collect the fluid directly from the wound bed over anextended area.

Such materials include cytokines, enzymes, nutrients for wound cells toaid proliferation, oxygen, and other molecules that are beneficiallyinvolved in wound healing, such as growth factors, and others havingbeneficial effects (which may be further enhanced) in causingchemotaxis.

In all embodiments of the apparatus of this first aspect of the presentinvention for aspirating, irrigating and/or cleansing wounds, aparticular advantage is the tendency of the wound dressing to conform tothe shape of the bodily part to which it is applied.

The wound dressing comprises a backing layer with a wound-facing facewhich is capable of forming a relatively fluid-tight seal or closureover a wound and

-   -   at least one inlet pipe for connection to a fluid supply tube or        recirculation tube, which passes through and/or under the        wound-facing face, and    -   and at least one outlet pipe for connection to a fluid offtake        tube, which passes through and/or under the wound-facing face,    -   the point at which the or each inlet pipe and the or each outlet        pipe passes through and/or under the wound-facing face forming a        relatively fluid-tight seal or closure.

The term ‘relatively fluid-tight seal or closure’ is used herein toindicate one which is fluid- and microbe-impermeable and permits apositive or negative pressure of up to 50% atm., more usually up to 15%atm. to be applied to the wound. The term ‘fluid’ is used herein toinclude gels, e.g. thick exudate, liquids, e.g. water, and gases, suchas air, nitrogen, etc.

The shape of the backing layer that is applied may be any that isappropriate to aspirating, irrigating and/or cleansing the wound acrossthe area of the wound.

Examples of such include a substantially flat film, sheet or membrane,or a bag, chamber, pouch or other structure of the backing layer, e.g.of polymer film, which can contain the fluid.

The backing layer may be a film, sheet or membrane, often with a(generally uniform) thickness of up to 100 micron, preferably up to 50micron, more preferably up to 25 micron, and of 10 micron minimumthickness.

Its largest cross-dimension may be up to 500 mm (for example for largetorso wounds), up to 100 mm (for example for axillary and inguinalwounds), and up to 200 mm for limb wounds (for example for chronicwounds, such as venous leg ulcers and diabetic foot ulcers.

Desirably the dressing is resiliently deformable, since this may resultin increased patient comfort, and lessen the risk of inflammation of awound.

Suitable materials for it include synthetic polymeric materials that donot absorb aqueous fluids, such as polyolefins, such as polyethylenee.g. high-density polyethylene, polypropylene, copolymers thereof, forexample with vinyl acetate and polyvinyl alcohol, and mixtures thereof;polysiloxanes; polyesters, such as polycarbonates; polyamides, e.g. 6-6and 6-10, and hydrophobic polyurethanes.

They may be hydrophilic, and thus also include hydrophilicpolyurethanes.

They also include thermoplastic elastomers and elastomer blends, forexample copolymers, such as ethyl vinyl acetate, optionally or asnecessary blended with high-impact polystyrene.

They further include elastomeric polyurethane, particularly polyurethaneformed by solution casting.

Preferred materials for the present wound dressing include thermoplasticelastomers and curable systems.

The backing layer is capable of forming a relatively fluid-tight seal orclosure over the wound and/or around the inlet and outlet pipe(s).

However, in particular around the periphery of the wound dressing,outside the relatively fluid-tight seal, it is preferably of a materialthat has a high moisture vapour permeability, to prevent maceration ofthe skin around the wound. It may also be a switchable material that hasa higher moisture vapour permeability when in contact with liquids, e.g.water, blood or wound exudate. This may, e.g. be a material that is usedin Smith & Nephew's Allevyn™, IV3000™ and OpSite™ dressings.

The periphery of the wound-facing face of the backing layer may bear anadhesive film, for example, to attach it to the skin around the wound.

This may, e.g. be a pressure-sensitive adhesive, if that is sufficientto hold the wound dressing in place in a fluid-tight seal around theperiphery of the wound-facing face of the wound dressing.

Alternatively or additionally, where appropriate a light switchableadhesive could be used to secure the dressing in place to preventleakage. (A light switchable adhesive is one the adhesion of which isreduced by photocuring. Its use can be beneficial in reducing the traumaof removal of the dressing.)

Thus, the backing layer may have a flange or lip extending around theproximal face of the backing layer, of a transparent or translucentmaterial (for which it will be understood that materials that are listedabove are amongst those that are suitable).

This bears a film of a light switchable adhesive to secure the dressingin place to prevent leakage on its proximal face, and a layer of opaquematerial on its distal face.

To remove the dressing and not cause excessive trauma in removal of thedressing, the layer of opaque material on the distal face of the flangeor lip extending around the proximal wound is removed prior toapplication of radiation of an appropriate wavelength to the flange orlip.

If the periphery of the wound dressing, outside the relativelyfluid-tight seal, that bears an adhesive film to attach it to the skinaround the wound, is of a material that has a high moisture vapourpermeability or is a switchable material, then the adhesive film, ifcontinuous, should also have a high or switchable moisture vapourpermeability, e.g. be an adhesive such as used in Smith & Nephew'sAllevyn™, IV3000™ and OpSite™ dressings.

Where a vacuum, is applied to hold the wound dressing in place in afluid-tight seal around the periphery of the wound-facing face of thewound dressing, the wound dressing may be provided with a siliconeflange or lip to seal the dressing around the wound; This removes theneed for adhesives and associated trauma to the patient's skin.

Where the interior of, and the flow of irrigant and/or wound exudate toand through, the dressing is under any significant positive pressure,which will tend to act at peripheral points to lift and remove thedressing off the skin around the wound.

In such use of the apparatus, it may thus be necessary to provide meansfor forming and maintaining such a seal or closure over the woundagainst such positive pressure on the wound, to act at peripheral pointsfor this purpose.

Examples of such means include light switchable adhesives, as above, tosecure the dressing in place to prevent leakage.

Since the adhesion of a light switchable adhesive is reduced byphotocuring, thereby reducing the trauma of removal of the dressing, afilm of a more aggressive adhesive may be used, e.g. on a flange, asabove.

Examples of suitable fluid adhesives for use in more extreme conditionswhere trauma to the patient's skin is tolerable include ones thatconsist essentially of cyanoacrylate and like tissue adhesives, appliedaround the edges of the wound and/or the proximal face of the backinglayer of the wound dressing, e.g. on a flange or lip.

Further suitable examples of such means include adhesive (e.g. withpressure-sensitive adhesive) and non-adhesive, and elastic andnon-elastic straps, bands, loops, strips, ties, bandages, e.g.compression bandages, sheets, covers, sleeves, jackets, sheathes, wraps,stockings and hose, e.g. elastic tubular hose or elastic tubularstockings that are a compressive fit over a limb wound to apply suitablepressure to it when the therapy is applied in this way; and inflatablecuffs, sleeves, jackets, trousers, sheathes, wraps, stockings and hosethat are a compressive fit over a limb wound to apply suitable pressureto it when the therapy is applied in this way.

Such means may each be laid out over the wound dressing to extend beyondthe periphery of the backing layer of the wound dressing, and asappropriate will be adhered or otherwise secured to the skin around thewound and/or itself and as appropriate will apply compression (e.g. withelastic bandages, stockings) to a degree that is sufficient to hold thewound dressing in place in a fluid-tight seal around the periphery ofthe wound,

Such means may each be integral with the other components of thedressing, in particular the backing layer.

Alternatively, it may be permanently attached or releasably attached tothe dressing, in particular the backing layer, with an adhesive film,for example, or these components may be a Velcro™, push snap ortwist-lock fit with each other.

The means and the dressing may be separate structures, permanentlyunattached to each other.

In a more suitable layout for higher positive pressures on the wound, astiff flange or lip extends around the periphery of the proximal face ofthe backing layer of the wound dressing as hereinbefore defined.

The flange or lip is concave on its proximal face to define a peripheralchannel or conduit.

It has a suction outlet that passes through the flange or lip tocommunicate with the channel or conduit and may be connected to a devicefor applying a vacuum, such as a pump or a piped supply of vacuum.

The backing layer may be integral with or attached, for example byheat-sealing, to the flange or lip extending around its proximal face.

To form the relatively fluid-tight seal or closure over a wound that isneeded and to prevent passage of irrigant and/or exudate under theperiphery of the wound-facing face of the wound dressing, in use of theapparatus, the dressing is set on the skin around the wound.

The device then applies a vacuum to the interior of the flange or lip,thus forming and maintaining a seal or closure acting at peripheralpoints around the wound against the positive pressure on the wound.

With all the foregoing means of attachment, and means for forming andmaintaining a seal or closure over the wound, against positive ornegative pressure on the wound at peripheral points around the wound,the wound dressing sealing periphery is preferably of a generally roundshape, such as an ellipse, and in particular circular.

To form the relatively fluid-tight seal or closure over a wound andaround the inlet pipe(s) and outlet pipe(s) at the point at which theypass through and/or under the wound-facing face, the backing layer maybe integral with these other components.

The components may alternatively just be a push, snap or twist-lock fitwith each other, or adhered or heat-sealed together.

The or each inlet pipe or outlet pipe may be in the form of an aperture,such as a funnel, hole, opening, orifice, luer, slot or port forconnection as a female member respectively to a mating end of

-   -   a fluid recirculation tube and/or fluid supply tube (optionally        or as necessary via means for forming a tube, pipe or hose, or        nozzle, hole, opening, orifice, luer, slot or port for        connection as a male member respectively to a mating end of    -   a fluid recirculation tube and/or fluid supply tube (optionally        or as necessary via means for flow switching between supply and        recirculation) or a fluid offtake tube.

Where the components are integral they will usually be made of the samematerial (for which it will be understood that materials that are listedabove are amongst those that are suitable).

Where, alternatively, they are a push, snap or twist-lock fit, the maybe of the same material or of different materials. In either case,materials that are listed above are amongst those that are suitable forall the components.

The or each pipe will generally pass through, rather than under thebacking layer. In such case, the backing layer may often have a rigidand/or resiliently inflexible or stiff area to resist any substantialplay between the or each pipe and the or each mating tube, ordeformation under pressure in any direction.

It may often be stiffened, reinforced or otherwise strengthened by aboss projecting distally (outwardly from the wound) around each relevanttube, pipe or hose, or nozzle, hole, opening, orifice, luer, slot orport for connection to a mating end of a fluid recirculation tube and/orfluid supply tube or fluid offtake tube.

Alternatively or additionally, where appropriate the backing layer mayhave a stiff flange or lip extending around the proximal face of thebacking layer to stiffen, reinforce or otherwise strengthen the backinglayer.

The wound dressing may not comprise any integer under the backing layerin the wound in use.

However, this may not provide a system to distribute irrigant over asufficient functional surface area to irrigate the wound at a practicalrate. To be suitable for use, in particular in chronic wound dialysis,with relatively high concentrations of materials that are deleterious towound healing, it may be advantageous to provide a system where woundirrigant and/or wound exudate may be distributed more evenly, or pass ina more convoluted path under the dressing over the wound bed.

Accordingly, one form of the dressing is provided with a ‘tree’ form ofpipes, tubes or tubules that radiate from an inlet manifold to the woundbed to end in apertures and deliver the circulating fluid directly tothe wound bed via the apertures. Similarly, there is an outlet manifoldfrom which tubules radiate and run to the wound bed to end in openingsand collect the fluid directly from the wound bed.

The pipes, etc. may radiate regularly or irregularly through the woundin use, respectively from the inlet or outlet manifold, althoughregularly may be preferred. A more suitable layout for deeper wounds isone in which the pipes, etc. radiate hemispherically and concentrically,to the wound bed.

For shallower wounds, examples of suitable forms of such layout of thepipes, etc. include ones in which the pipes, etc. radiate in a flattenedhemiellipsoid and concentrically, to the wound bed.

Other suitable forms of layout of the pipes, etc. include one which havepipes, tubes or tubules extending from the inlet pipe(s) and/or outletpipe(s) at the point at which they pass through and/or under thewound-facing face of the backing layer to run over the wound bed. Thesemay have a blind bore with perforations, apertures, holes, openings,orifices, slits or slots along the pipes, etc.

These pipes, etc. then effectively form an inlet pipe manifold thatdelivers the circulating fluid directly to the wound bed or outlet pipeor collects the fluid directly from the wound respectively.

It does so via the holes, openings, orifices, slits or slots in thetubes, pipes, tubules, etc. over most of the wound bed under the backinglayer.

It may be desirable that the tubes, pipes or tubules are resilientlyflexible, e.g. elastomeric, and preferably soft, structures with goodconformability in the wound and the interior of the wound dressing.

When the therapy is applied in this way, the layout of the tubes, pipes,tubules, etc. may depend on the depth and/or capacity of the wound.

Thus, for shallower wounds, examples of suitable forms of such layout ofthe tubes, pipes, tubules, etc. include ones that consist essentially ofone or more of the tubes, etc in a spiral.

A more suitable layout for deeper wounds when the therapy is applied inthis way may be one which comprises one or more of the tubes, etc in ahelix or spiral helix.

Other suitable layouts for shallower wounds include one which haveblind-bore, perforated inlet pipe or outlet pipe manifolds thatcirculate fluid in the wound when the dressing is in use.

One or both of these may be such a form, the other may be, e.g. one ormore straight blind-bore, perforated radial tubes, pipes or nozzles.

Another suitable layout is one in which

-   -   an inlet pipe and/or outlet pipe manifold that delivers the        circulating fluid directly to the wound bed or collects the        fluid directly from the wound respectively    -   via inlet and/or outlet tubes, pipes or tubules,    -   and the inlet manifold and/or outlet manifold is formed by slots        in layers permanently attached to each other in a stack, and    -   the inlet and/or outlet tubes, pipes or tubules are formed by        apertures through layers permanently attached to each other in a        stack. (In FIG. 10A there is shown an exploded isometric view of        such a stack, which is non-limiting.)

As also mentioned herein, the backing layer that is applied may be anythat is appropriate to the present system of therapy and permits apositive or negative pressure of up to 50% atm., more usually up to 25%atm. to be applied to the wound.

It is thus often a microbe-impermeable film, sheet or membrane, which issubstantially flat, depending on any pressure differential on it, andoften with a (generally uniform) thickness similar to such films orsheets used in conventional wound dressings, i.e. up to 100 micron,preferably up to 50 micron, more preferably up to 25 micron, and of 10micron minimum thickness.

The backing layer may often have a rigid and/or resiliently inflexibleor stiff area to resist any substantial play between other componentsthat are not mutually integral, and may be stiffened, reinforced orotherwise strengthened, e.g. by a projecting boss.

Such a form of dressing would not be very conformable to the wound bed,and may effectively form a chamber, hollow or cavity defined by abacking layer and the wound bed under the backing layer.

It may be desirable that the interior of the wound dressing conform tothe wound bed, even for a wound in a highly exuding state. Accordingly,one form of the dressing is provided with a wound filler under thebacking layer.

This is favourably a resiliently flexible, e.g. elastomeric, andpreferably soft, structure with good conformability to wound shape.

It is urged by its own resilience against the backing layer to applygentle pressure on the wound bed.

The wound filler may be integral with the other components of thedressing, in particular the backing layer.

Alternatively, it may be permanently attached to them/it, with anadhesive film, for example, or by heat-sealing, e.g. to a flange or lipextending from the proximal face, so a not to disrupt the relativelyfluid-tight seal or closure over the wound that is needed.

Less usually, the wound filler is releasably attached to the backinglayer, with an adhesive film, for example, or these components may be apush, snap or twist-lock fit with each other.

The wound filler and the backing layer may be separate structures,permanently unattached to each other.

The wound filler may be or comprise a solid integer, favourably aresiliently flexible, e.g. elastomeric, and preferably soft, structurewith good conformability to wound shape.

Examples of suitable forms of such wound fillers are foams formed of asuitable material, e.g. a resilient thermoplastic. Preferred materialsfor the present wound dressing include reticulated filtrationpolyurethane foams with small apertures or pores.

Alternatively or additionally, it may be in the form of, or comprise oneor more conformable hollow bodies defined by a film, sheet or membrane,such as a bag, chamber, pouch or other structure, filled with a fluid orsolid that urges it to the wound shape.

The film, sheet or membrane, often has a (generally uniform) thicknesssimilar to that of films or sheets used in conventional wound dressingbacking layers.

That is, up to 100 micron, preferably up-to 50 micron, more preferablyup to 25 micron, and of 10 micron minimum thickness, and is oftenresiliently flexible, e.g. elastomeric, and preferably soft.

Such a filler is often integral with the other components of thedressing, in particular the backing layer, or permanently attached tothem/it, with an adhesive film, for example, or by heat-sealing, e.g. toa flange

Examples of suitable fluids contained in the hollow body or bodiesdefined by a film, sheet or membrane include gases, such as air,nitrogen and argon, more usually air, at a small positive pressure aboveatmospheric; and liquids, such as water, saline.

Examples also include gels, such as silicone gels, e.g. CaviCare™ gel,or preferably cellulosic gels, for example hydrophilic cross-linkedcellulosic gels, such as Intrasite™ cross-linked materials. Examplesalso include aerosol foams, where the gaseous phase of the aerosolsystem is air or an inert gas, such as nitrogen or argon, more usuallyair, at a small positive pressure above atmospheric; and solidparticulates, such as plastics crumbs.

Of course, if the backing layer is a sufficiently conformable and/ore.g. an upwardly dished sheet, the backing layer may lie under the woundfiller, rather than vice versa.

In this type of layout, in order for the wound filler to urge the wounddressing towards the wound bed, it will usually have to be firmlyadhered or otherwise releasably attached to the skin around the wound.This is especially the case in those embodiments where the wound fillerand the backing layer are separate structures, permanently unattached toeach other.

In such a layout for deeper wounds when the therapy is applied in thisway, the means for such attachment may also form and maintain a seal orclosure over the wound.

Where the filler is over the backing layer, and the fluid inlet pipe(s)and outlet pipe(s) pass through the wound-facing face of the backinglayer, they may run through or around the wound filler over the backinglayer.

One form of the dressing is provided with a wound filler under thebacking layer that is or comprises a resiliently flexible, e.g.elastomeric, and preferably soft, hollow body defined by a film, sheetor membrane, such as a bag, chamber, pouch or other structure, withapertures, holes, openings, orifices, slits or slots, or tubes, pipes,tubules or nozzles. It communicates with at least one inlet or outletpipe through at least one aperture, hole, opening, orifice, slit orslot.

The fluid contained in the hollow body may then be the circulating fluidin the apparatus.

The hollow body or each of the hollow bodies then effectively forms aninlet pipe or outlet pipe manifold that delivers the circulating fluiddirectly to the wound bed or collects the fluid directly from the woundrespectively via the holes, openings, orifices, slits or slots, or thetubes, pipes or hoses, etc. in the film, sheet or membrane.

When the therapy is applied in this way, the type of the filler may alsobe largely determined by the depth and/or capacity of the wound.

Thus, for shallower wounds, examples of suitable wound fillers as acomponent of a wound dressing include ones that consist essentially ofone or more conformable hollow bodies defining an inlet pipe and/oroutlet pipe manifold that delivers the circulating fluid directly to thewound bed or collects the fluid directly from the wound.

A more suitable wound filler for deeper wounds when the therapy isapplied in this way may be one which comprises one or more conformablehollow bodies defined by, for example a polymer film, sheet or membrane,that at least partly surround(s) a solid integer. This may provide asystem with better rigidity for convenient handling.

Unless the wound filler under the backing layer effectively forms aninlet pipe or outlet pipe manifold with a direct connection between theinlet pipe(s) and outlet pipe(s) at the point at which they pass throughand/or under the wound-facing face and the wound bed is present, inorder for aspiration and/or irrigation of the wound bed to occur, it isappropriate for one or more bores, channels, conduits, passages, pipes,tubes, tubules and/or spaces, etc. to run from the point at which thefluid inlet pipe(s) and outlet pipe(s) pass through and/or under thewound-facing face of the backing layer through or around the woundfilter filler under the backing layer.

Less usually, the wound filler is an open-cell foam with pores that mayform such bores, channels, conduits, passages and/or spaces through thewound filler under the backing layer.

Where the filler is or comprises one or more conformable hollow bodiesdefined by, for example a polymer film, sheet or membrane, it may beprovided with means for admitting fluids to the wound bed under thewound dressing.

These may be in the form of pipes, tubes, tubules or nozzles runningfrom the point at which the fluid inlet pipe(s) and outlet pipe(s) passthrough and/or under the wound-facing face of the backing layer throughor around the wound filler under the backing layer.

All of the suitable layouts for shallower wounds that compriseblind-bore, perforated inlet pipe or outlet pipe manifolds thatcirculate fluid in the wound when the dressing is in use, that aredescribed hereinbefore, may be used under a wound filler under thebacking layer.

In brief, suitable layouts include ones where one or both manifolds areannular or toroidal (regular, e.g. elliptical or circular, orirregular), optionally with blind-bore, perforated radial tubes, pipesor nozzles, branching from the annulus or torus; and/or

-   -   in a meandering, tortuous, winding, zigzag, serpentine or        boustrophedic (i.e. in the manner of a ploughed furrow) pattern,        or    -   defined by slots in and apertures through layers attached to        each other in a stack.

The inlet and/or outlet tubes, the fluid recirculation tube and thefluid supply tube, etc. may be of conventional type, e.g. of ellipticalor circular cross-section, and may suitably have a uniform cylindricalbore, channel, conduit or passage throughout their length.

Depending on the desired fluid volume flow rate of irrigant and/or woundexudate from the wound, and the desired amount in recirculation,suitably the largest cross-dimension of the bore may be up to 10 mm forlarge torso wounds, and up to 2 mm for limb wounds.

The tube walls should suitably thick enough to withstand any positive ornegative pressure on them, in particular if the volume of irrigantand/or wound exudate from the wound in recirculation is increased bycontinuing addition to it of wound exudate, and/or fluid passing from acleansing fluid through a selectively permeable integer, for example thepolymer film, sheet or membrane of a two-phase system, such as andialysis unit. However, as noted below with regard to pumps, the primepurpose of such tubes is to convey fluid irrigant and exudate throughthe length of the apparatus flow path, rather than to act as pressurevessels. The tube walls may suitably be at least 25 micron thick.

The bore or any perforations, apertures, holes, openings, orifices,slits or slots along the pipes, etc. or in the hollow body or each ofthe hollow bodies may be of small cross-dimension.

They may then effectively form a macroscopic and/or microscopic filterfor particulates including cell debris and micro-organisms, whilstallowing proteins and nutrients to pass through.

Such tubes, pipes or hoses, etc. through and/or around the filler,whether the latter is a solid integer and/or one or more resilientlyflexible or conformable hollow bodies, are described in further detailhereinbefore in connection with the inlet pipe(s) and outlet pipe(s).

The whole length of the apparatus for aspirating, irrigating and/orcleansing wounds should be microbe-impermeable once the wound dressingis over the wound in use.

It is desirable that the wound dressing and the interior of theapparatus for aspirating, irrigating and/or cleansing wounds of thepresent invention is sterile.

The fluid may be sterilised in the fluid reservoir and/or the rest ofthe system in which the fluid recirculates, including the means forfluid cleansing, by ultraviolet, gamma or electron beam irradiation.This way, in particular reduces or eliminates contact of internalsurfaces and the fluid with any sterilising agent.

Examples of other methods of sterilisation of the fluid also includee.g. the use of

-   -   ultrafiltration through microapertures or micropores, e.g. of        0.22 to 0.45 micron maximum cross-dimension, to be selectively        impermeable to microbes; and    -   fluid antiseptics, such as solutions of chemicals, such as        chlorhexidine and povidone iodine; metal ion sources, such as        silver salts, e.g. silver nitrate; and hydrogen peroxide;    -   although the latter involve contact of internal surfaces and the        fluid with the sterilising agent.

It may be desirable that the interior of the wound dressing, the rest ofthe system in which the fluid recirculates, and/or the wound bed, evenfor a wound in a highly exuding state, are kept sterile after the fluidis sterilised in the fluid reservoir, or that at least naturallyoccurring microbial growth is inhibited.

Thus, materials that are potentially or actually beneficial in thisrespect may be added to the irrigant initially, and as desired theamount in recirculation increased by continuing addition.

Examples of such materials include antibacterial agents (some of whichare listed above), and antifungal agents.

Amongst those that are suitable are, for example triclosan, iodine,metronidazole, cetrimide, chlorhexidine acetate, sodium undecylenate,chlorhexidine and iodine.

Buffering agents, such as potassium dihydrogen phosphate/disodiumhydrogen phosphate may be added to adjust the pH, as may localanalgesics/anaesthetics, such as lidocaine/lignocaine hydrochloride,xylocaine (adrenaline, lidocaine) and/or anti-inflammatories, to reducewound pain or inflammation or pain associated with the dressing.

It is also desirable to provide a system in which physiologically activecomponents of the exudate that are beneficial to wound healing are notremoved before or after the application of fluid cleansing.

This may occur, e.g. by the passive deposition of materials that arebeneficial in promoting wound healing, such as proteins, e.g. growthfactors.

This may occur at any point in the flow path, e.g. in at least one inletor outlet pipe.

The deposition of materials that are beneficial in promoting woundhealing may be combated as follows:

-   -   a) extra materials may be added to the irrigant initially, and        as desired the amount in recirculation increased by continuing        addition, or    -   b) a repellent coating may be used at any point or on any        integer in the recirculation path in direct contact with the        fluid, e.g. on the means for fluid cleansing or any desired tube        or pipe.

Examples of coating materials for surfaces over which the circulatingfluid passes include

-   -   anticoagulants, such as heparin, and    -   high surface tension materials, such as PTFE, and polyamides,    -   which are useful for growth factors, enzymes and other proteins        and derivatives.

The apparatus of the invention for aspirating, irrigating and/orcleansing wounds is provided with means for admitting fluids directly orindirectly to the wound under the wound dressing in the form of a fluidsupply tube to a fluid reservoir.

The fluid reservoir may be of any conventional type, e.g. a tube, bag(such as a bag typically used for blood or blood products, e.g. plasma,or for infusion feeds, e.g. of nutrients), chamber, pouch or otherstructure, e.g. of polymer film, which can contain the irrigant fluid.

The reservoir may be made of a film, sheet or membrane, often with a(generally uniform) thickness similar to that of films or sheets used inconventional wound dressing backing layers, i.e. up to 100 micron,preferably up to 50 micron, more preferably up to 25 micron, and of 10micron minimum thickness, and is often a resiliently flexible, e.g.elastomeric, and preferably soft, hollow body.

In all embodiments of the apparatus the type and material of the tubesthroughout the apparatus of the invention for aspirating, irrigatingand/or cleansing wounds and the fluid reservoir will be largelydetermined by their function.

To be suitable for use, in particular on chronic timescales, thematerial should be non-toxic and biocompatible, inert to any activecomponents, as appropriate of the irrigant from the fluid reservoirand/or wound exudate in the apparatus flow path, and, in any use of atwo-phase system dialysis unit, of the dialysate that moves into thecirculating fluid in the apparatus.

When in contact with irrigant fluid, it should not allow any significantamounts of extractables to diffuse freely out of it in use of theapparatus.

It should be sterilisable by ultraviolet, gamma or electron beamirradiation and/or with fluid antiseptics, such as solutions ofchemicals, fluid- and microbe-impermeable once in use, and flexible.

Examples of suitable materials for the fluid reservoir include syntheticpolymeric materials, such as polyolefins, such as polyethylene, e.g.high-density polyethylene and polypropylene.

Suitable materials for the present purpose also include copolymersthereof, for example with vinyl acetate and mixtures thereof. Suitablematerials for the present purpose further include medical gradepoly(vinyl chloride).

Notwithstanding such polymeric materials, the fluid reservoir will oftenhave a stiff area to resist any substantial play between it andcomponents that are not mutually integral, such as the fluid supply tubetowards the wound dressing, and may be stiffened, reinforced orotherwise strengthened, e.g. by a projecting boss.

The device for moving fluid through the wound and means for fluidcleansing may be any appropriate for this purpose, and may act at anyappropriate point for this purpose.

It may apply a positive or negative pressure to the wound, although itsprime purpose is to move fluid (irrigant from the fluid reservoir and/orwound exudate through the length of the apparatus flow path, rather thanto apply a positive or negative pressure to the wound.

If applied to the fluid in recirculation in the fluid recirculation tubeupstream of and towards the wound dressing and/or the fluid in the fluidsupply tube towards the wound dressing (optionally or as necessary viameans for flow switching between supply and recirculation), it willusually apply positive pressure (i.e. above-atmospheric pressure) to thewound bed.

Often the means for fluid cleansing is (most appropriately for itspurpose) downstream of the wound dressing, and provides the highestresistance in the flow path. This is especially the case where the meansfor fluid cleansing is a single-phase system, e.g. with ultrafiltrationthrough microapertures or micropores, thus enhancing applied positivepressure to the wound.

Where the device is applied to the fluid in recirculation in the fluidrecirculation tube and/or the fluid in the fluid offtake tube downstreamof and away from the wound dressing, it will usually apply negativepressure (i.e. below-atmospheric pressure or vacuum) to the wound bed.

Again, often the means for fluid cleansing is (most appropriately forits purpose) downstream of the wound dressing, and provides the highestresistance in the flow path, thus enhancing applied negative pressure tothe wound.

The following types of pump may be used as desired:

-   -   reciprocating pumps, such as:        -   shuttle pumps—with an oscillating shuttle mechanism to move            fluids at rates from 2 to 50 ml per minute;        -   diaphragm pumps—where pulsations of one or two flexible            diaphragms displace liquid while check valves control the            direction of the fluid flow.        -   piston pumps—where pistons pump fluids through check valves,            in particular for positive and/or negative pressure on the            wound bed;    -   rotary pumps, such as:        -   centrifugal pumps        -   flexible impeller        -   pumps—where elastomeric impeller traps fluid between            impeller blades and a moulded housing that sweeps fluid            through the pump housing. progressing cavity        -   pumps—with a cooperating screw rotor and stator, in            particular for higher-viscosity and particulate-filled            exudate;        -   rotary vane pumps—with rotating vaned disk attached to a            drive shaft moving fluid without pulsation as it spins. The            outlet can be restricted without damaging the pump.        -   peristaltic pumps—with peripheral rollers on rotor arms            acting on a flexible fluid circulation tube to urge fluid            current flow in the tube in the direction of the rotor.        -   vacuum pumps—with pressure regulators.

The type and/or capacity of the device will be largely determined by

-   -   a) the appropriate or desired fluid volume flow rate of irrigant        and/or wound exudate from the wound, and    -   b) whether it is appropriate or desired to apply a positive or        negative pressure to the wound bed, and the level of such        pressure to the wound bed        for optimum performance of the wound healing process, and by        factors such as portability, power consumption and isolation        from contamination.

Such a device may also suitably be one that is capable of pulsed,continuous, variable, reversible and/or automated and/or programmablefluid movement. It may in particular be a pump of any of these types.

In practice, even from a wound in a highly exuding state, such a rate ofexudate flow is only of the order of up to 75 microlitres/cm²/hr (wherecm² refers to the wound area), and the fluid can be highly mobile (owingto the proteases present). Exudate levels drop and consistency changesas the wound heals, e.g. to a level for the same wound that equates to12.5-25 microlitres/cm²/hr.

Where materials deleterious to wound healing are removed by a two-phasesystem (see below), such as a dialysis unit, fluid is also potentiallylost to the system through the means for fluid cleansing.

This may occur, e.g. through a dialysis polymer film, sheet or membranewhich is also permeable to water, in addition to materials deleteriousto wound healing.

The balance of fluid in recirculation may thus further decrease, but maybe adjusted to minimise this undesired loss in a routine manner asdescribed hereinbefore.

Hence, it will be seen that the circulating fluid from the wound willtypically contain a preponderance of irrigant over wound exudate inrecirculation from the fluid reservoir.

The type and/or capacity of the device will thus be largely determinedin this respect by the appropriate or desired fluid volume flow rate ofirrigant, rather than that of exudate, from the wound.

In practice, such a rate of flow of total irrigant and/or wound exudatewill be of the order of 1 to 1000, e.g. 3 to 300, and less preferably 1to 10 ml/cm²/24 hour, where the cm² refers to the wound area.

The volume of irrigant and/or wound exudate in recirculation may varyover a wide range, but will typically be e.g. 1 to 8 l. (for example forlarge torso wounds), 200 to 1500 ml (for example for axillary andinguinal wounds), and 0.3 to 300 ml for limb wounds when the therapy isapplied in this way.

In practice, suitable pressures are of the order of up to 25% atm suchas up to 10% atm. positive or negative pressure on the wound bed, theapparatus being operated as a closed recirculating system.

The higher end of these ranges are potentially more suitable forhospital use, where relatively high % pressures and/or vacua may be usedsafely under professional supervision.

The lower end is potentially more suitable for home use, whererelatively high % pressures and/or vacua cannot be used safely withoutprofessional supervision, or for field hospital use.

The device may be a peristaltic pump or diaphragm pump, e.g. preferablya small portable diaphragm or peristaltic pump. These are preferredtypes of pump, in order in particular to reduce or eliminate contact ofinternal surfaces and moving parts of the pump with (chronic) woundexudate, and for ease of cleaning.

It may suitably be one that applies positive pressure to the woundand/or the means for fluid cleansing. A preferred pump when the appliedpressure is positive is a peristaltic pump, e.g. a small, portableperistaltic pump, mounted upstream of the means for fluid cleansing.

Where the pump is a peristaltic pump, this may be e.g. an Instech ModelP720 miniature peristaltic pump, with a flow rate: of 0.2-180 ml/hr anda weight of <0.5 k. This is potentially useful for home and fieldhospital use.

The pump may suitably be one that applies negative pressure to the woundand/or the means for fluid cleansing.

A preferred pump when the applied pressure is negative is a diaphragmpump, e.g. a small, portable diaphragm pump, mounted downstream of thedressing or the means for fluid cleansing.

Where the pump is a diaphragm pump, and preferably a small portablediaphragm pump, the one or two flexible diaphragms that displace liquidmay each be, for example a polymer film, sheet or membrane, that isconnected to means for creating the pulsations. This may be provided inany form that is convenient, inter alia as a piezoelectric transducer, acore of a solenoid or a ferromagnetic integer and coil in which thedirection of current flow alternates, a rotary cam and follower, and soon.

The outlet from the dressing passes to the means for fluid cleansing forremoval of materials deleterious to wound healing from wound exudate,and in turn to the fluid recirculation tube(s).

The apparatus of the invention for aspirating, irrigating and/orcleansing wounds is provided with means for fluid cleansing, which maybe

-   -   a) a single-phase system, such as an ultrafiltration unit, or a        chemical absorption and/or adsorption unit; or    -   b) a two-phase system, such as a dialysis unit, or a biphasic        extraction unit.

In the former, circulating fluid from the wound and the fluid reservoirpasses through a self-contained system in which materials deleterious towound healing are removed and the cleansed fluid, still containingmaterials that are beneficial in promoting wound healing are returned tothe wound.

The single-phase system may be of any conventional type.

Examples of the means for fluid cleansing in such a system include amacro- or microfiltration unit, which appropriately comprises one ormore macroscopic and/or microscopic filters.

These are to retain particulates, e.g. cell debris and micro-organisms,allowing proteins and nutrients to pass through.

Alternatively, they also include an ultrafiltration unit, such as a onein which the cleansing integer is a filter for materials deleterious towound healing, for example a high throughput, low protein-bindingpolymer film, sheet or membrane which is selectively impermeable tomaterials deleterious to wound healing, which are removed and thecleansed fluid, still containing materials that are beneficial inpromoting wound healing is passed by it.

The membrane may preferably be of a hydrophilic polymeric material, suchas a cellulose acetate-nitrate mixture, polyvinylidene chloride, and,for example hydrophilic polyurethane.

Examples of less preferred materials include hydrophobic materials alsoincluding polyesters, such as polycarbonates, PTFE, and polyamides, e.g.6-6 and 6-10, and hydrophobic polyurethanes, and quartz and glass fibre.

It has microapertures or micropores, the maximum cross-dimension ofwhich will largely depend on the species that are to be selectivelyremoved in this way and those to which it is to be permeable.

The former may be removed with microapertures or micropores, e.g.typically with a maximum cross-dimension in the range of 20 to 700micron, e.g. 20 to 50 nm (for example for undesired proteins), 50 to 100nm, 100 to 250 nm, 250 to 500 nm and 500 to 700 nm.

The filter integer may be a flat sheet or a membrane of a polymericmaterial in a more convoluted form, e.g. in the form of elongatestructure, such as pipes, tubules, etc.

The system may be a chemical adsorption unit, for example one in which aparticulate, such as a zeolite, or a layer, e.g. of a functionalisedpolymer has sites on its surface that are capable of removing materialsdeleterious to wound healing on passing the circulating fluid from thewound and the fluid reservoir over them.

The materials may be removed, e.g. by destroying or binding thematerials that are deleterious to wound healing, by, for examplechelators and/or ion exchangers, degraders, which may be enzymes.

Examples of such also include less specific chemical absorption and/oradsorption units, for example one in which a physical absorbent, such asactivated carbon or a zeolite, has non-specific sites on its surfacethat are capable of removing materials deleterious to wound healing onpassing the circulating fluid from the wound and the fluid reservoirover them.

The cleansing integer, for example the polymer film, sheet or otherchemical absorption and/or adsorption means, etc should of course becapable of removing materials deleterious to wound healing at apractical rate for a given capacity of the apparatus flow path and theflow rate of irrigant.

In the two-phase system, circulating fluid from the wound and the fluidreservoir in indirect or (less usually, direct) contact with a secondfluid (dialysate) phase, more usually a liquid.

Thus, in one form, a biphasic liquid extraction unit, the second fluidphase is (usually) a liquid that is immiscible with the circulatingfluid from the dressing, over a surface of which the circulating fluidpasses in direct contact with the cleansing fluid. Materials deleteriousto wound healing are removed into the dialysate, and the cleansed fluid,still containing materials that are beneficial in promoting woundhealing, is returned via the recirculation tube to the wound bed.

Examples of such means for fluid cleansing include those wherein thesecond fluid (dialysate) phase is perfluorodecalin and like materials

Alternatively, where appropriate it may be provided in a form in whichthe two fluids (recirculation fluid and dialysate) are separated by asignificantly two-dimensional integer, for example a polymer film, sheetor membrane or hollow fibre or filament that is permeable to materialsin the circulating fluid in the apparatus.

Again, materials deleterious to wound healing are removed into thedialysate, and the cleansed fluid, still containing materials that arebeneficial in promoting wound healing, is returned via the recirculationtube to the wound bed.

In either form in which the two-phase system, such as a dialysis unit,is provided, in use typically the dialysate moves past the circulatingfluid in the apparatus in a co- or preferably counter-current direction.

Pumps, such as peristaltic pumps, and/or valves control the direction ofthe two fluid flows.

However, the cleansing fluid may less usually be static, although thismay not provide a system with sufficient (dynamic) surface area toremove materials deleterious to wound healing from wound exudate at apractical rate.

Typical dialysate flow rates in a dialytic means for fluid cleansing inthe present apparatus for aspirating, irrigating and/or cleansing woundsare those used in the conventional type of two-phase system, such as adialysis unit for systemic therapy.

The integer may be a film, sheet or membrane, often of the same type,and of the same (generally uniform) thickness, as those used inconventional two-phase system, such as a dialysis unit for systemictherapy.

The film, sheet or membrane may be substantially flat, and depending onany pressure differential across it may require other materials on or init to stiffen, reinforce or otherwise strengthen it.

However, this may not provide a system with sufficient functionalsurface area to remove materials deleterious to wound healing from woundexudate at a practical rate.

To be suitable for use, in particular in chronic wound dialysis, withrelatively high concentrations of materials that are deleterious towound healing, it may be advantageous to provide a system in which thefilm, sheet or membrane of a polymeric material is in a more convolutedform.

This may be in the form of elongate structures, such as pipes, tubeshollow fibres or filaments or tubules of a round cross-section, e.g.elliptical or circular, e.g. in a parallel array with spacestherebetween.

The wound irrigant and/or wound exudate may recirculate through theinside and the cleansing fluid may pass into the spaces between adjacentpipes, tubes or tubules in a co- or preferably counter-currentdirection, or vice versa.

Again, materials deleterious to wound healing are removed into thedialysate, and the cleansed fluid, still containing materials that arebeneficial in promoting wound healing, is returned via the recirculationtube to the wound.

Where the means for fluid cleansing is a two-phase system, e.g. in theform of a dialysis unit, or a biphasic extraction unit, the circulatingfluid from the wound and the fluid reservoir passes across one surfacesof a significantly two-dimensional integer, for example a polymer film,sheet or membrane which is selectively permeable to materialsdeleterious to wound healing.

These are removed by passing a cleansing fluid across the other surfaceof the integer. The integer may be a film, sheet or membrane that isselectively permeable to the foregoing materials deleterious to woundhealing.

Examples of these as above include

-   -   oxidants, such as free radicals, e.g. peroxide and superoxide;    -   iron II and iron III;    -   all involved in oxidative stress on the wound bed;    -   proteases, such as serine proteases, e.g. elastase and thrombin;        cysteine proteases; matrix metalloproteases, e.g. collagenase;        and carboxyl (acid) proteases;    -   endotoxins, such as lipopolysaccharides;    -   autoinducer signalling molecules, such as homoserine lactone        derivatives, e.g. oxo-alkyl derivatives;    -   inhibitors of angiogenesis such as thrombospondin-1 (TSP-1),        Plasminogen activator inhibitor, or angiostatin (plasminogen        fragment)    -   pro-inflammatory cytokines such as tumour necrosis factor alpha        (TNFα) and interleukin 1 beta (IL-1β), and    -   inflammatories, such as lipopolysaccharides, and e.g. histamine.

Examples of suitable materials for the film, sheet or membrane(typically in the form of conformable hollow bodies defined by the film,sheet or membrane, such as the structures described hereinbefore)include natural and synthetic polymeric materials.

The membrane may be of one or more hydrophilic polymeric materials, suchas a cellulose derivative, e.g. regenerated cellulose, a cellulosemono-, di- or tri-esters, such as cellulose mono-, di- or tri-acetate,benzyl cellulose and Hemophan, and mixtures thereof.

Examples of other materials include hydrophobic materials, such asaromatic polysulphones, polyethersulphones, polyetherether-sulphones,polyketones, polyetherketones and polyetherether-ketones, andsulphonated derivatives thereof, and mixtures thereof.

Examples of other materials include hydrophobic materials, such aspolyesters, such as polycarbonates and polyamides, e.g. 6-6 and 6-10;polyacrylates, including, e.g. poly(methyl methacrylate),polyacrylonitrile and copolymers thereof, for exampleacrylonitrile-sodium metallosulphonate copolymers; and poly(vinylidenechloride).

Suitable materials for the present membranes include thermoplasticpolyolefins, such as polyethylene e.g. high-density polyethylene,polypropylene, copolymers thereof, for example with vinyl acetate andpolyvinyl alcohol, and mixtures thereof.

The dialysis membrane should have a molecular weight cut off (MWCO)chosen to allow selective perfusion of species deleterious to woundhealing that have been targeted for removal from the wound. For example,perfusion of the serine protease elastase (molecular weight 25900Dalton) would require a membrane with MWCO >25900 Dalton. The MWCOthreshold can be varied to suit each application between 1 and 3000000Dalton.

Preferably, the MWCO should be as close as possible to this weight toexclude interference by larger competitor species.

For example, such a membrane with MWCO >25900 Dalton does not allow anysignificant amounts of the antagonist to elastase, alpha-1-antitrypsin(AAT) (molecular weight 54000 Dalton), which occurs naturally in wounds,to diffuse freely out of the wound fluid into the dialysate. Theinhibitor, which is beneficial in promoting chronic wound healing,remains in contact with the wound bed, and can act beneficially on it,whilst the elastase that is deleterious to wound healing is removed.

Such use of the present apparatus is, e.g. favourable to the woundhealing process in chronic wounds, such as diabetic foot ulcers, andespecially decubitus pressure ulcers.

As noted hereinafter, antagonists, for example degrading enzymes, orsequestrating agents for elastase on the dialysate side of the membrane,may be used to enhance the removal of this protease from wound exudate.

Where it is desired to remove several different materials that aredeleterious to wound healing, it may be advantageous to provide a systemof modules in series, each of which removes a different material. Thisallows incompatible cleansing materials to be used on the same fluidand/or wound exudates.

Preferably any such system is a conventional automated, programmablesystem which can cleanse the wound irrigant and/or wound exudate withminimal supervision.

As noted above in more detail, fluid passes from a cleansing fluidthrough a selectively permeable integer.

This may be the typical permeable polymer film, sheet or membrane of atwo-phase system, such as a dialysis unit.

Additionally, solutes or disperse phase species will pass from thedialysate into the irrigant and/or wound exudate through the dialysispolymer film, sheet or membrane.

This property may be used to perfuse materials beneficial to woundhealing into the irrigant and/or exudate from a dialysate.

In this less conventional type of infusion feed, a broad spectrum ofspecies will usually pass into the exudate and/or irrigant fluid fromthe dialysate.

These include

-   -   ionic species, such as bicarbonate;    -   vitamins, such as ascorbic acid (vitamin C) and vitamin E, and        stable derivatives thereof, and mixtures thereof; to relieve        oxidative stress on the wound bed;    -   pH buffering agents, such as potassium dihydrogen        phosphate/disodium hydrogen phosphate,    -   local analgesics/anaesthetics, such as lidocainealignocaine        hydrochloride and xylocaine (adrenoline lidocaine) and/or        anti-inflammatories, to reduce wound pain or inflammation or        pain associated with the dressing    -   nutrients to aid proliferation of wound cells, such as amino        acids, sugars, low molecular weight tissue building blocks and        trace elements; and other cell culture medium species; and    -   gases, such as air, nitrogen, oxygen and/or nitric oxide.

For the purposes of fluid cleansing in the apparatus of the presentinvention, both the single-phase system, such as an ultrafiltrationunit, and two-phase system, such as a dialysis unit, may have captive(non-labile, insoluble and/or immobilised) species such as thefollowing, bound to an insoluble and/or immobilised) substrate overand/or through which the irrigant and/or wound exudate from, the wounddressing passes in turn to the fluid recirculation tube(s):

-   -   antioxidants and free radical scavengers, such as        3-hydroxytyramine (dopamine), ascorbic acid (vitamin C), vitamin        E and glutathione, and stable derivatives thereof, and mixtures        thereof; to relieve oxidative stress on the wound bed;    -   metal ion chelators and/or ion exchangers, such as transition        metal ion chelators, such as iron III chelators (Fe III is        involved in oxidative stress on the wound bed), such as        desferrioxamine (DFO), 3-hydroxytyramine (dopamine);    -   iron III reductants;    -   protease inhibitors, such as TIMPs and alpha 1-antitrypsin        (AAT); serine protease inhibitors, such as        4-(2-aminoethyl)-benzene sulphonyl fluoride (AEBSF, PefaBloc)        and Nα-p-tosyl-L-lysine chloro-methyl ketone (TLCK) and        ε-aminocaproyl-p-chlorobenzylamide; cysteine protease        inhibitors; matrix metalloprotease inhibitors; and carboxyl        (acid) protease inhibitors;    -   sacrificial redox materials that are potentially or actually        beneficial in promoting wound healing, by the removal of        materials that trigger the expression into wound exudate of        redox-sensitive genes that are deleterious to wound healing;    -   autoinducer signalling molecule degraders, which may be enzymes;        and    -   anti-inflammatory materials to bind or destroy        lipopolysaccharides, e.g. peptidomimetics

Other physiologically active components of the exudate that aredeleterious to wound healing may be removed in this way.

These may be removed with suitable chelators and/or ion exchangers,degraders, which may be enzymes, or other species.

The following types of functionalised substrate has sites on its surfacethat are capable of removing materials deleterious to wound healing onpassing the circulating fluid from the wound and the fluid reservoirover them:

heterogeneous resins, for example silica-supported reagents such as:

-   metal scavengers,-   3-(diethylenetriamino)propyl-functionalised silica gel-   2-(4-(ethylenediamino)benzene)ethyl-functionalised silica gel-   3-(mercapto)propyl-functionalised silica gel-   3-(1-thioureido)propyl-functionalised silica gel-   triamine tetraacetate-functionalised silica gel-   or electrophilic scavengers, 4-carboxybutyl-functionalised silica    gel-   4-ethyl benzenesulfonyl chloride-functionalised silica gel-   propionyl chloride-functionalised silica gel-   3-(isocyano)propyl-functionalised silica gel-   3-(thiocyano)propyl-functionalised silica gel-   3-(2-succinic anhydride)propyl-functionalised silica gel-   3-(maleimido)propyl-functionalised silica gel-   or nucleophilic scavengers,-   3-aminopropyl-functionalised silica gel-   3-(ethylenediamino)-functionalised silica gel-   2-(4-(ethylenediamino)propyl-functionalised silica gel-   3-(diethylenetriamino)propyl-functionalised silica gel-   4-ethyl-benzenesulfonamide-functionalised silica gel-   2-(4-toluenesulfonyl hydrazino)ethyl-functionalised silica gel-   3-(mercapto)propyl-functionalised silica gel-   dimethylsiloxy-functionalised silica gel-   or base or acid scavengers,-   3-(dimethylamino)propyl-functionalised silica gel-   3-(1,3,4,6,7,8-hexahydro-2H-pyrimido-[1,2-α]pyrimidino)propyl-functionalised    silica gel-   3-(1-imidazol-1-yl)propyl-functionalised silica gel-   3-(1-morpholino)propyl-functionalised silica gel-   3-(1-piperazino)propyl-functionalised silica gel-   3-(1-piperidino)propyl-functionalised silica gel-   3-(4,4′-trimethyidipiperidino)propyl-functionalised silica gel-   2-(2-pyridyl)ethyl-functionalised silica gel-   3-(trimethylammonium)propyl-functionalised silica gel-   or the reagents,-   3-(1-cyclohexylcarbodiimido)propyl-functionalised silica gel-   TEMPO-functionalised silica gel-   2-(diphenylphosphino)ethyl-functionalised silica gel-   2-(3,4-cyclohexyidiol)propyl-functionalised silica gel-   3-(glycidoxy)propyl-functionalised silica gel-   2-(3,4-epoxycyclohexyl)propyl-functionalised silica gel-   1-(allyl)methyl-functionalised silica gel-   4-bromopropyl-functionalised silica gel-   4-bromophenyl-functionalised silica gel-   3-chloropropyl-functionalised silica gel-   4-benzyl chloride-functionalised silica gel-   2-(carbomethoxy)propyl-functionalised silica gel-   3-(4-nitrobenzamido)propyl-functionalised silica gel-   3-(ureido)propyl-functionalised silica gel-   or any combinations of the above.

The use of such captive (non-labile, insoluble and/or immobilised)species, such as the foregoing, bound to an insoluble and immobilised)substrate over and/or through which the irrigant and/or wound exudatefrom, the wound dressing passes has been described hereinbefore assuitable for the means for fluid cleansing.

However, they may additionally, where appropriate, be used in any partof the apparatus that is in contact with the irrigant and/or woundexudate, but often within the dressing, for removal of materialsdeleterious to wound healing from wound.

The means for fluid cleansing may additionally, where appropriate,comprise one or more macroscopic and/or microscopic filters.

These are to retain particulates, e.g. cell debris and micro-organisms,allowing proteins and nutrients to pass through.

Alternatively, a less conventional type of two-phase system (see above),such as a dialysis unit, may be used as the means for fluid cleansing.In this type, the dialysis polymer film, sheet or membrane is not aninteger selectively permeable to materials deleterious to wound healing,such as proteases, such as serine proteases, e.g. elastase and thrombin;cysteine protease; matrix metalloproteases, e.g. collagenase; andcarboxyl (acid) proteases;

-   -   endotoxins, such as lipopolysaccharides;    -   inhibitors of angiogenesis such as thrombospondin-1 (TSP-1),        plasminogen activator inhibitor, or angiostatin (plasminogen        fragment);    -   pro-inflammatory cytokines such as tumour necrosis factor alpha        (TNFα) and interleukin 1 beta (IL-1β),    -   oxidants, such as free radicals, e.g., e.g. peroxide and        superoxide; and metal ions, e.g. iron II and iron III, all        involved in oxidative stress on the wound bed.

It will however also permit components of the exudate from a woundand/or irrigant fluid that may be larger or smaller molecules, but arebeneficially involved in wound healing to pass into and through it.

In the dialysate, or preferably in one or more solid structural integerswith at least one surface in contact with the dialysate, in the meansfor fluid cleansing, there are one or more materials that can removematerials deleterious to wound healing from wound exudate, by beingantagonists to such species, for example enzymes or others, such asprotease inhibitors, such as serine protease inhibitors, such as4-(2-aminoethyl)-benzene sulphonyl fluoride (AEBSF, PefaBloc) andNa-p-tosyl-L-lysine chloromethyl ketone (TLCK) andε-aminocaproyl-ρ-chlorobenzylamide; cysteine protease inhibitors; matrixmetalloprotease inhibitors; and carboxyl (acid) protease inhibitors;

-   -   binders and/or degraders, such as anti-inflammatory materials to        bind or destroy lipopolysaccharides, e.g. peptidomimetics;    -   anti-oxidants, such as 3-hydroxytyramine (dopamine), ascorbic        acid (vitamin C), vitamin E and glutathione, and stable        derivatives thereof, and mixtures thereof; to relieve oxidative        stress on the wound bed; and    -   chelators and/or ion exchanges, such as desferrioxamine (DFO),        3-hydroxytyramine (dopamine),

They further include peptides (including cytokines, e.g. bacterialcytokines, such as α-amino-γ-butyrolactone and L-homocarnosine); and

-   -   sacrificial redox materials that are potentially or actually        beneficial in promoting wound healing, such as iron III        reductants; and/or regeneratable materials of this type, such as        glutathione redox systems; and other physiologically active        components.

In use of the two-phase system dialysis unit, of this less conventionaltype, a broad spectrum of species will usually pass into the dialysatefrom the exudate.

Some (mainly ionic) species will pass from the dialysate into theirrigant and/or wound exudate through the dialysis polymer film, sheetor membrane that is not very selectively permeable to materialsdeleterious to wound healing.

The components of the exudate from a wound and/or irrigant fluid willdiffuse freely to and fro through it.

If (preferably) none of the dialysate is voided to waste, e.g. to acollection bag, a steady state concentration equilibrium is eventuallyset up between the dialysate and the irrigant and/or wound exudate,which is ‘topped up’ from the wound dressing.

Circulating wound fluid aids in the quicker attainment of thisequilibrium of materials beneficial in promoting wound healing.

It also returns them to the site where they can be potentially of mostbenefit, i.e. the wound bed.

The target materials deleterious to wound healing also pass into thedialysate from the exudate through the dialysis polymer film, sheet ormembrane that is not very selectively permeable to materials deleteriousto wound healing.

Unlike the other components of the exudate from a wound and/or irrigantfluid, the target materials deleterious to wound healing come intocontact with the dialysate, or preferably with one or more solidstructural integers with at least one surface in the dialysate, and areremoved by the appropriate antagonists, binders and/or degraders,chelators and/or ion exchangers and redox agents, etc. The cleansedfluid, still containing some materials that are beneficial in promotingwound healing, is returned to the recirculation tube.

Unlike the other components of the exudate from a wound and/or irrigantfluid the target materials are constantly removed from the dialysate,very little of these species will pass from the dialysate into theirrigant and/or wound exudate, and a steady state concentrationequilibrium is not set up, even if the species are constantly ‘toppedup’ from the wound dressing.

It is believed that circulating wound fluid aids in removal fromrecirculation of the materials deleterious to wound healing from woundexudate, whilst retaining materials that are beneficial in promotingwound healing in contact with the wound.

A particular advantage of this form of the two-phase system, is thatwhere a material that can remove materials deleterious to wound healingfrom wound exudate is (cyto)toxic or bioincompatible, or not inert toany components that are beneficial in promoting wound healing, thesystem does not allow any significant amounts of antagonist to diffusefreely out of the dialysate into the irrigant fluid. The active materialcan act beneficially on the fluid however.

The film sheet or membrane is preferably a dialysis membrane ofmolecular weight cut off (MWCO) (as conventionally defined) chosen toallow perfusion of species targeted for sequestration or destruction.

For example, sequestration of the serine protease elastase (molecularweight 25900 Dalton) would require a membrane with MWCO >25900 Dalton.

The MWCO threshold can be varied to suit each application between 1 and3000000 Dalton. Preferably, the MWCO should be as close as possible tothis weight to exclude sequestering interference by larger competitorspecies.

Both the single-phase system, such as an ultrafiltration unit, andtwo-phase system, such as a dialysis unit, may be in modular form thatis relatively easily demountable from the apparatus of the invention.The system may suitably comprise one or more such modules.

The conduits through which respectively

-   -   a) the irrigant and/or wound exudate passes from the wound        dressing and    -   b) the cleansed fluid, still containing materials that are        beneficial in promoting wound healing, is returned to the        recirculation tube, and    -   c) (in the case where the means is provided in the form of a        two-phase system, such as an dialysis unit) through which the        cleansing fluid enters and exits the means preferably have means        for, on module disconnection and withdrawal,    -   i) switching off the flow and    -   ii) providing an immediate fluid-tight seal or closure over the        ends of the conduits and the cooperating tubes in the rest of        the apparatus of the invention so exposed,        to prevent continuing passage of irrigant and/or exudate and        cleansed fluid, and cleansing fluid.

The apparatus of the invention for aspirating, irrigating and/orcleansing wounds is provided with means for bleeding the offtake and/orrecirculation tubes, such as a regulator, such as a valve or othercontrol device for bleeding fluids from the wound.

The device for moving fluid through the wound and means for fluidcleansing is used to move irrigant to the wound dressing and apply thedesired positive or negative pressure on the wound bed.

The desired balance of fluid in recirculation tube will typically beregulated by means of

-   -   a) the means for bleeding the offtake and/or recirculation        tubes,    -   b) the means for flow switching between supply and        recirculation, and/or    -   c) the means for moving fluid over the wound bed and through the        means for fluid cleansing,        as appropriate.

Thus, e.g. if

-   -   a) the apparatus for aspirating, irrigating and/or cleansing        wounds is a single-phase system, such as an ultrafiltration        unit,    -   b) the wound is not in a highly exuding state and    -   c) it is not appropriate or desired to admit fluid into the        wound from the fluid reservoir,        there is no or negligible change in the balance of fluid in        recirculation.

Once it has been primed throughout, e.g. to the desired positive ornegative pressure on the wound bed, the apparatus may be operated as aclosed recirculating system.

The means for flow switching between supply and recirculation tubes isset to close the wound to the fluid reservoir via the fluid supply tube,and the means for bleeding the offtake and/or recirculation tubes arealso closed.

If

-   -   a) the apparatus for aspirating, irrigating and/or cleansing        wounds is a single-phase system, such as an ultrafiltration        unit,    -   b) the wound is in a highly exuding state and/or    -   c) it is appropriate or desired to admit fluid into the wound        from the fluid reservoir,        there is a positive change in the balance of fluid in        recirculation.

Once it has been primed throughout, e.g. to the desired positive ornegative pressure on the wound bed, the apparatus cannot be operated asa closed recirculating system, without the pressure to the wound bedincreasing, possibly undesirably.

The means for bleeding the offtake and/or recirculation tubes must beopened to some extent to relieve positive pressure on the wound bed. Thebleed-off may be voided to waste, e.g. to a collection bag.

Materials that are beneficial in promoting wound healing may be lost tothe site where they can be potentially of most benefit, i.e. the woundbed, when the therapy is applied in this way.

However, the balance of fluid in recirculation may be routinely adjustedto minimise this undesired loss.

The factors that determine the balance of fluid in recirculation in anapparatus with a two-phase system means for fluid cleansing in the formof a dialysis unit, or a biphasic extraction unit have been describedhereinbefore in detail hereinbefore in connection with the operation ofthe apparatus. It is sufficient to note here that at some point aftersteady state recirculation established through the length of theapparatus flow path, it may be necessary that any bleed valve is opened,if overall the fluid level is increasing by transfer from the dialysateto an undesirable extent.

Other combinations, and the necessary adjustments to maintain thedesired balance of fluid in recirculation tube by means of

-   -   a) the means for bleeding the offtake and/or recirculation        tubes,    -   b) the means for flow switching between supply and        recirculation, and/or    -   c) the means for moving fluid        will be apparent to the skilled person.

The outlet from the means for bleeding the offtake and/or recirculationtubes may be collected and monitored and used to diagnose the status ofthe wound and/or its exudate.

The waste reservoir may be of any conventional type, e.g. a tube, bag(such as a bag typically used as an ostomy bag), chamber, pouch or otherstructure, e.g. of polymer film, which can contain the irrigant fluidthat has been bled off. In all embodiments of the apparatus, the typeand material of the waste reservoir will be largely determined by itsfunction. To be suitable for use, the material need only befluid-impermeable once in use, and flexible.

Examples of suitable materials for the fluid reservoir include syntheticpolymeric materials, such as polyolefins, such as poly (vinylidenechloride).

Suitable materials for the present purpose also include polyethylene,e.g. high-density polyethylene, polypropylene, copolymers thereof, forexample with vinyl acetate and mixtures thereof.

In a second aspect of the present invention there is provided aconformable wound dressing, characterised in that it comprises a backinglayer with a wound-facing face which is capable of forming a relativelyfluid-tight seal or closure over a wound and has

-   -   at least one inlet pipe for connection to a fluid supply tube,        which passes through and/or under the wound-facing face, and    -   at least one outlet pipe for connection to a fluid offtake tube,        which passes through and/or under the wound-facing face,    -   the point at which the or each inlet pipe and the or each outlet        pipe passes through and/or under the wound-facing face forming a        relatively fluid-tight seal or closure over the wound.

The dressing is advantageously provided for use in a bacteria-proofpouch.

Examples of suitable forms of such wound dressings are as described byway of example hereinbefore.

It is desirable

-   -   a) to obviate at least some of the disadvantages of known        aspiration and/or irrigation therapies, and    -   b) to provide a system of therapy which        -   i) can remove materials deleterious to wound healing from            wound exudate, whilst retaining materials that are            beneficial in promoting wound healing in contact with the            wound bed, and/or        -   ii) which allows fluids containing active amounts of            materials that are beneficial in promoting wound healing to            pass into and/or through the wound in contact with the wound            bed.

Thus, in a third aspect of the present invention there is provided amethod of treating wounds to promote wound healing using the apparatusfor aspirating, irrigating and/or cleansing wounds of the presentinvention.

BRIEF DESCRIPTION OF THE DRAWINGS

The present invention will now be described by way of example only withreference to the accompanying drawings in which:

FIG. 1 is a schematic view of an apparatus for aspirating, irrigatingand/or cleansing a wound according to the first aspect of the presentinvention.

It has a single-phase system means for fluid cleansing in the form of anultrafiltration unit.

FIG. 2 is a schematic view of an apparatus for aspirating, irrigatingand/or cleansing a wound according to the first aspect of the presentinvention.

It has a two-phase system means for fluid cleansing in the form of adialysis unit, or a biphasic extraction unit.

FIGS. 3A to 7B are cross-sectional views of conformable wound dressings,of the second aspect of the present invention for aspirating and/orirrigating wounds.

In these, FIGS. 3A to 7A are cross-sectional plan views of the wounddressings, and FIGS. 3B to 7B are cross-sectional side views of thewound dressings.

FIGS. 8A to 10C are various views of inlet and outlet manifold layoutsfor the wound dressings of the second aspect of the present inventionfor respectively delivering fluid to, and collecting fluid from, thewound.

FIG. 11 is a schematic view of an apparatus for aspirating, irrigatingand/or cleansing a wound according to the first aspect of the presentinvention.

It has a single-phase system means for fluid cleansing in the form of anultrafiltration unit.

FIG. 12 is a schematic view of an apparatus for aspirating, irrigatingand/or cleansing a wound according to the first aspect of the presentinvention.

It has a two-phase system means for fluid cleansing in the form of adialysis unit, or a biphasic extraction unit.

FIGS. 13A to 26 are cross-sectional views of conformable wounddressings, of the second aspect of the present invention for aspiratingand/or irrigating wounds.

FIG. 27 is a schematic view of another apparatus for aspirating,irrigating and/or cleansing a wound according to the first aspect of thepresent invention.

It has a single-phase system means for fluid cleansing in the form of anultrafiltration unit.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT

Referring to FIG. 1, the apparatus (1) for aspirating, irrigating and/orcleansing wounds comprises

-   -   a conformable wound dressing (2), having    -   a backing layer (3) which is capable of forming a relatively        fluid-tight seal or closure (4) over a wound (5) and    -   one inlet pipe (6) for connection to a fluid supply tube (7),        which passes through the wound-facing face of the backing layer        (5) at (8), and    -   one outlet pipe (9) for connection to a fluid offtake tube (10),        which passes through the wound-facing face at (11),    -   the points (8), (11) at which the inlet pipe and the outlet pipe        passes through and/or under the wound-facing face forming a        relatively fluid-tight seal or closure over the wound,    -   the inlet pipe being connected via means for flow switching        between supply and recirculation, here a T-valve (14), by the        fluid supply tube (7) to a fluid reservoir (12) and to a fluid        recirculation tube (13) having a means for bleeding the tube,        here a bleed T-valve (16) to waste, e.g. to a collection bag        (not shown),    -   the outlet pipe (9) being connected to a fluid offtake tube        (10), connected in turn to    -   means for fluid cleansing (17), here in the form of an        ultrafiltration unit, connected to the inlet pipe (6) via the        fluid recirculation tube (13) and T-valve (14), and    -   a device for moving fluid through the wound and means for fluid        cleansing (17), here a peristaltic pump (18), e.g. preferably a        small portable peristaltic pump, acting on the fluid circulation        tube (13) with the peripheral rollers on its rotor (not shown)        to apply a low negative pressure on the wound.

The ultrafiltration unit (17) is a single-phase system. In this thecirculating fluid from the wound and the fluid reservoir passes througha self-contained system in which materials deleterious to wound healingare removed and the cleansed fluid, still containing materials that arebeneficial in promoting wound healing, is returned via the recirculationtube to the wound bed.

(In a variant of this apparatus, there are two inlet pipes (6), whichare connected respectively to a fluid supply tube (7) and fluidrecirculation tube (13), respectively having a first valve (19) foradmitting fluid into the wound from the fluid reservoir (12) and asecond valve (20) for admitting fluid into the wound from therecirculation tube.

Usually in use of the apparatus, when the first valve (19) is open, thesecond valve (20) is shut, and vice versa.)

In use of the apparatus (1), the valve (16) is opened to a collectionbag (not shown), and the T-valve (14) is turned to admit fluid from thefluid reservoir to the wound dressing through the fluid supply tube (7)and inlet pipe (6). (In the variant of this apparatus having two inletpipes (6), which are connected respectively to a fluid supply tube (7)and fluid recirculation tube (13), the first valve (19) for admittingfluid into the wound from the fluid reservoir (12) is opened and thesecond valve (20) is shut, and vice versa.)

The pump (18) is started to nip the fluid recirculation tube (13) withthe peripheral rollers on its rotor (not shown) to apply a low positivepressure on the wound. It is allowed to run until the apparatus isprimed throughout the whole length of the apparatus flow path and excessfluid is voided to waste via the bleed T-valve (16) into the collectionbag (not shown).

The T-valve (14) is then turned to switch from supply and recirculation,i.e. is set to close the wound to the fluid reservoir (12) but to admitfluid into the wound from the fluid recirculation tube (13), and thebleed T-valve (16) is simultaneously closed.

(In the variant of this apparatus, where there are two inlet pipes (6),which are connected respectively to a fluid supply tube (7) and fluidrecirculation tube (13), the first valve (19) is closed and arecirculating system set up by opening the second valve (20) foradmitting fluid into the wound from the recirculation tube (13).

The circulating fluid from the wound and the fluid reservoir (12) passesthrough the ultrafiltration unit (17). Materials deleterious to woundhealing are removed and the cleansed fluid, still containing materialsthat are beneficial in promoting wound healing, is returned via therecirculation tube (13) to the wound bed.

The recirculation of fluid may be continued as long as desired.

Switching between supply and recirculation is then reversed, by turningthe T-valve (14) to admit fluid from the fluid reservoir to the wounddressing through the fluid supply tube (7) and inlet pipe (6).

(In the variant of this apparatus having two inlet pipes (6), which areconnected respectively to a fluid supply tube (7) and fluidrecirculation tube (13), the first valve (19) for admitting fluid intothe wound from the fluid reservoir (12) is opened and the second valve(20) is shut, and vice versa.)

The bleed valve (16) is simultaneously opened, so that fresh fluidflushes the recirculating system.

The running of the pump (18) may be continued until the apparatus isflushed, when it and the fluid recirculation is stopped.

If, e.g. the wound is in a highly exuding state, there is a positivechange in the balance of fluid in recirculation. It may be necessary tobleed fluid from recirculation, by opening the bleed T-valve (16) tobleed fluid from the recirculation tube (13).

Referring to FIG. 2, the apparatus (21) is a variant of that of FIG. 1,with identical, and identically numbered, components, except for themeans for fluid cleansing, which is in the form of a two-phase system,here a dialysis unit (23).

In this, there is one system through which the circulating fluid fromthe wound and the fluid reservoir passes and from which deleteriousmaterials are removed by selectively permeable contact with a secondsystem, through which passes a cleansing fluid.

The dialysis unit (23) thus has an internal polymer film, sheet ormembrane (24), selectively permeable to materials deleterious to woundhealing, which divides it into

-   -   a) a first chamber (25), through which passes a cleansing fluid        across one surface of the polymer film, sheet or membrane, and    -   b) a second chamber (26), through which passes the circulating        fluid from the wound and the fluid reservoir (12), and from        which deleterious materials are removed

The dialysis unit (23) thus has a dialysate inlet pipe (28) connectingto a dialysate supply tube (29) which passes to a peristaltic pump (38),e.g. preferably a small portable peristaltic pump, acting on thedialysate supply tube (29) with the peripheral rollers on its rotor (notshown) to supply cleansing fluid across the surface of the polymer film,sheet or membrane (28) in the first chamber (25) from a dialysatereservoir (not shown) via a valve (34).

The dialysis unit (23) also has a dialysate outlet pipe (30) connectingto a dialysate outlet tube (31) which passes to waste via a second bleedT-valve (36) into, e.g. a collection bag (not shown).

Operation of this apparatus is similar to that of FIG. 1, except for thedialysis unit (23), in that at some point after the irrigation system isprimed and steady state recirculation established through the length ofthe apparatus flow path, the valve (34) and second bleed valve (36) areopened.

The pump (38) is started to nip fluid dialysate tube (29) with theperipheral rollers on its rotor (not shown) to pump cleansing fluid tothe first chamber from a dialysate reservoir (not shown) and out towaste via the bleed valve (36) into the collection bag (not shown).

The dialysis unit (23) is a module (or scrubbing cartridge) with asubstrate that changes colour to indicate the presence of detrimentalfactors in the cleansed fluid, and that the scrubbing cartridge isexhausted and should be renewed.

Referring to FIGS. 3A to 6B, each dressing (41) is in the form of aconformable body defined by a microbe-impermeable film backing layer(42) with a uniform thickness of 25 micron, with a wound-facing face(43) which is capable of forming a relatively fluid-tight seal orclosure over a wound.

The backing layer (42) extends in use on a wound over the skin aroundthe wound. On the proximal face of the backing layer (43) on the overlap(44), it bears an adhesive film (45), to attach it to the skinsufficiently to hold the wound dressing in place in a fluid-tight sealaround the periphery of the wound-facing face (43) of the wounddressing.

There is one inlet pipe (46) for connection to a fluid supply tube (notshown), which passes through and/or under the wound-facing face (43),and one outlet pipe (47) for connection to a fluid offtake tube (notshown), which passes through and/or under the wound-facing face (43).

Referring to FIGS. 3A and 3B, one form of the dressing is provided witha wound filler (48) under a circular backing layer (42).

This comprises a generally frustroconical, toroidal conformable hollowbody, defined by a membrane (49) which is filled with a fluid, here airor nitrogen, that urges it to the wound shape.

The filler (48) may be permanently attached to the backing layer with anadhesive film (not shown) or by heat-sealing.

The inlet pipe (46) and outlet pipe (47) are mounted centrally in thebacking layer (42) above the central tunnel (50) of the toroidal hollowbody (48) and each passes through the backing layer (42), and eachextends in pipes (51) and (52) respectively through the tunnel (50) ofthe toroidal hollow body (48) and then radially in diametricallyopposite directions under the body (48).

This form of the dressing is a more suitable layout for deeper wounds.

Referring to FIGS. 4A and 4B, a more suitable form for shallower woundsis shown. This comprises a circular backing layer (42) and a circularupwardly dished first membrane (61) with apertures (62) that ispermanently attached to the backing layer (42) by heat-sealing to form acircular pouch (63).

The pouch (63) communicates with the inlet pipe (46) through a hole(64), and thus effectively forms an inlet pipe manifold that deliversthe circulating fluid directly to the wound when the dressing is in use.

An annular second membrane (65) with openings (66) is permanentlyattached to the backing layer (42) by heat-sealing to form an annularchamber (67) with the layer (42).

The chamber (67) communicates with the outlet pipe (47) through anorifice (68), and thus effectively forms an outlet pipe manifold thatcollects the fluid directly from the wound when the dressing is in use.

Referring to FIGS. 5A and 5B, a variant of the dressing of FIGS. 4A and4B that is a more suitable form for deeper wounds is shown.

This comprises a circular backing layer (42) and a filler (69), in theform of an inverted frustroconical, solid integer, here a resilientelastomeric foam, formed of a thermoplastic, or preferably across-linked plastics foam.

It may be permanently attached to the backing layer (42), with anadhesive film (not shown) or by heat-sealing.

A circular upwardly dished sheet (70) lies under and conforms to, but isa separate structure, permanently unattached to, the backing layer (42)and the solid integer (69).

A circular upwardly dished first membrane (71) with apertures (72) ispermanently attached to the sheet (70) by heat-sealing to form acircular pouch (73) with the sheet (70).

The pouch (73) communicates with the inlet pipe (46) through a hole(74), and thus effectively forms an inlet pipe manifold that deliversthe circulating fluid directly to the wound when the dressing is in use.

An annular second membrane (75) with openings (76) is permanentlyattached to the sheet (70) by heat-sealing to form an annular chamber(77) with the sheet (70).

The chamber (77) communicates with the outlet pipe (47) through anorifice (78), and thus effectively forms an outlet pipe manifold thatcollects the fluid directly from the wound when the dressing is in use.

Alternatively, where appropriate the dressing may be provided in a formin which the circular upwardly dished sheet (70) functions as thebacking layer and the solid filler (69) sits on the sheet (70) as thebacking layer, rather than under it. The filler (69) is held in placewith an adhesive film or tape, instead of the backing layer (42).

Referring to FIGS. 6A and 6B, a dressing that is a more suitable formfor deeper wounds is shown.

This comprises a circular backing layer (42) and a filler (79), in theform of an inverted generally hemispherical integer, here a resilientelastomeric foam or a hollow body filled with a fluid, here a gel thaturges it to the wound shape, and permanently attached to the backinglayer with an adhesive film (not shown) or by heat-sealing.

The inlet pipe (46) and outlet pipe (47) are mounted peripherally in thebacking layer (42).

A circular upwardly dished sheet (80) lies under and conforms to, but isa separate structure, permanently unattached to, the backing layer (42)and the filler (79).

A circular upwardly dished bilaminate membrane (81) has a closed channel(82) between its laminar components, with

-   -   perforations (83) along its length on the outer surface (84) of        the dish formed by the membrane (81) and    -   an opening (85) at the outer end of its spiral helix, through        which the channel (82) communicates with the inlet pipe (46),    -   and thus effectively forms an inlet pipe manifold that delivers        the circulating fluid directly to the wound when the dressing is        in use.

The membrane (81) also has apertures (86) between and along the lengthof the turns of the channel (82).

The inner surface (87) of the dish formed by the membrane (81) ispermanently attached at its innermost points (88) with an adhesive film(not shown) or by heat-sealing to the sheet (80). This defines a matingclosed spirohelical conduit (89).

At the outermost end of its spiral helix, the conduit (89) communicatesthrough an opening (90) with the outlet pipe (47) and is thuseffectively an outlet manifold to collect the fluid directly from thewound via the apertures (86).

Referring to FIGS. 7A and 7B, one form of the dressing is provided witha circular backing layer (42). A first (larger) inverted hemisphericalmembrane (92) is permanently attached centrally to the layer (42) byheat-sealing to form a hemispherical chamber (94) with the layer (42). Asecond (smaller) concentric hemispherical membrane (93) within the firstis permanently attached to the layer (42) by heat-sealing to form ahemispherical pouch (95). The pouch (95) communicates with the inletpipe (46) and is thus effectively an inlet manifold, from which pipes(97) radiate hemispherically and run to the wound bed to end inapertures (98). The pipes (97) deliver the circulating fluid directly tothe wound bed via the apertures (98).

The chamber (94) communicates with the outlet pipe (47) and is thuseffectively an outlet manifold from which tubules (99) radiatehemispherically and run to the wound bed to end in openings (100). Thetubules (99) collect the fluid directly from the wound via the openings(100).

Referring to FIGS. 8A to 8D, one form of the dressing is provided with asquare backing layer (42) and

-   -   first tube (101) extending from the inlet pipe (46), and    -   second tube (102) extending from the outlet pipe (47)    -   at the points at which they pass through the backing layer, to        run over the wound bed.

These pipes (101), (102) have a blind bore with orifices (103), (104)along the pipes (101), (102). These pipes (101), (102) respectively forman inlet pipe or outlet pipe manifold that delivers the circulatingfluid directly to the wound bed or collects the fluid directly from thewound respectively via the orifices.

In FIGS. 8A and 8D, one layout of each of the pipes (101), (102) asinlet pipe and outlet pipe manifolds is a spiral.

In FIG. 8B, the layout is a variant of that of FIGS. 8A and 8B, with thelayout of the inlet manifold (101) being a full or partial torus, andthe outlet manifold (102) being a radial pipe.

Referring to FIG. 8C, there is shown another suitable layout in whichthe inlet manifold (101) and the outlet manifold (102) run alongsideeach other over the wound bed in a boustrophedic pattern, i.e. in themanner of ploughed furrows.

Referring to FIGS. 9A to 9D, there are shown other suitable layouts fordeeper wounds, which are the same as shown in FIGS. 8a to 8d . Thesquare backing layer (42) however has a wound filler (110) under, andmay be permanently attached to, the backing layer (42), with an adhesivefilm (not shown) or by heat-sealing, which is an inverted hemisphericalsolid integer, here a resilient elastomeric foam, formed of athermoplastic, preferably a cross-linked plastics foam.

Under the latter is a circular upwardly dished sheet (111) whichconforms to, but is a separate structure, permanently unattached to, thesolid filler (110). Through the sheet (111) pass the inlet pipe (46) andthe outlet pipe (47), to run over the wound bed. These pipes (101),(102) again have a blind bore with orifices (103), (104) along the pipes(101), (102).

Alternatively (as in FIGS. 5A and 5B), where appropriate the dressingmay be provided in a form in which the circular upwardly dished sheet(111) functions as the backing layer and the solid filler (110) sits onthe sheet (42) as the backing layer, rather than under it. The filler(110) is held in place with an adhesive film or tape, instead of thebacking layer (42).

In FIGS. 10A to 10C, inlet and outlet manifolds for the wound dressingsfor respectively delivering fluid to, and collecting fluid from, thewound, are formed by slots in and apertures through layers permanentlyattached to each other in a stack.

Thus, in FIG. 10A there is shown an exploded isometric view of an inletmanifold and outlet manifold stack (120) of five square coterminousthermoplastic polymer layers, being first to fifth layers (121) to(125), each attached with an adhesive film (not shown) or byheat-sealing to the adjacent layer in the stack (120).

The topmost (first) layer (121) (which is the most distal in thedressing in use) is a blank square capping layer.

The next (second) layer (122), shown in FIG. 10B out of the manifoldstack (120), is a square layer, with an inlet manifold slot (126)through it. The slot (126) runs to one edge (127) of the layer (122) forconnection to a mating end of a fluid inlet tube ((not shown), andspreads into four adjacent branches (128) in a parallel array withspaces therebetween.

The next (third) layer (123) is another square layer, with inletmanifold apertures (129) through the layer (123) in an array such thatthe apertures (129) are in register with the inlet manifold slot (126)through the second layer (122) (shown in FIG. 10b ).

The next (fourth) layer (124), shown in FIG. 10C out of the manifoldstack (120), is another square layer, with inlet manifold apertures(130) through the layer (124) in an array such that the apertures (130)are in register with the apertures (129) through the third layer (123).

It also has an outlet manifold slot (131) through it.

The slot (131) runs to one edge (132) of the layer (124) on the oppositeside of the manifold stack (120) from the edge (127) of the layer (122),for connection to a mating end of a fluid outlet tube (not shown).

It spreads into three adjacent branches (133) in a parallel array in thespaces between the apertures (130) in the layer (124) and in registerwith the spaces between the apertures (129) in the layer (122).

The final (fifth) layer (125) is another square layer, with inletmanifold apertures (134) through the layer (125) in an array such thatthe apertures (134) are in register with the inlet manifold apertures(130) through the fourth layer (124) (in turn in register with theapertures (129) through the third layer (123). It also has outletmanifold apertures (135) in the layer (125) in an array such that theapertures (135) are in register with the outlet manifold slot (131) inthe fourth layer (124).

It will be seen that, when the layers (121) to (125) are attachedtogether to form the stack (120), the topmost (first) layer (121), theinlet manifold slot (126) through the second layer (122), and the thirdlayer (123) cooperate to form an inlet manifold in the second layer(122), which is in use is connected to a mating end of a fluid inlettube (not shown).

The inlet manifold slot (126) through the second layer (122), and theinlet manifold apertures (129), (130) and (134) through the layers(123), (124) and (125), all being mutually in register, cooperate toform inlet manifold conduits though the third to fifth layers (123),(124) and (125) between the inlet manifold in the second layer (122) andthe proximal face (136) of the stack (120).

The third layer (121), the outlet manifold slot (131) through the fourthlayer (124), and the fifth layer (125) cooperate to form an outletmanifold in the fourth layer (124), which is in use is connected to amating end of a fluid outlet tube (not shown).

The outlet manifold slot (131) through the fourth layer (124), and theoutlet manifold apertures (135) through the fifth layer (125), beingmutually in register, cooperate to form outlet manifold conduits thoughthe fifth layer (125) between the outlet manifold in the fourth layer(124) and the proximal face (136) of the stack (120).

Referring to FIG. 11, the apparatus (1) for aspirating, irrigatingand/or cleansing wounds is a variant of the apparatus (1) of FIG. 1.

It has bypass (711) around the pump (17), as a protection of the pumpagainst any blockage in the system.

It is activated automatically by appropriate means, e.g. it is normallyblocked by a bursting disc (not shown), or a pressure-activatedmotorised valve. An alternative to the by-pass (711) is a pressuresensor in the system that will detect excessive load or pressure, andshut down the pump. Referring to FIG. 12, the apparatus (1) foraspirating, irrigating and/or cleansing wounds is a variant of theapparatus (1) of FIG. 2.

The latter is a two-phase system with a dialysis unit (21), but is onein which dialytic fluid passes only once across the surface of thedialytic membrane (28) in the first chamber (25) from a dialysatereservoir (not shown) to waste via a second bleed T-valve (36) into,e.g. a collection bag (not shown).

This variant has a dialysate recirculation tube (811) running between afirst T-valve (816) on the inlet side of the dialysate pump (23) and asecond T-valve (817) to permit the pump (23) to recirculate thedialysate once the circuit is primed in multiple passes through thedialysis unit (21).

The operation of the system will be apparent to the skilled person.Referring to FIGS. 13 to 15, these forms of the dressing are providedwith a wound filler (348) under a circular backing layer (342).

This comprises respectively a generally downwardly domed or toroidal, oroblately spheroidal conformable hollow body, defined by a membrane (349)which is filled with a fluid, here air or nitrogen, that urges it to thewound shape.

The filler (348) is permanently attached to the backing layer via a boss(351), which is e.g. heat-sealed to the backing layer (342).

An inflation inlet pipe (350), inlet pipe (346) and outlet pipe (347)are mounted centrally in the boss (351) in the backing layer (342) abovethe hollow body (348). The inflation inlet pipe (350) communicates withthe interior of the hollow body (348), to permit inflation of the body(348). The inlet pipe (346) extends in a pipe (352) effectively throughthe hollow body (348). The outlet pipe (347) extends radiallyimmediately under the backing layer (342).

In FIGS. 13A and 13B, the pipe (352) communicates with an inlet manifold(353), formed by a membrane (361) with apertures (362) that ispermanently attached to the filler (348) by heat-sealing. It is filledwith foam (363) formed of a suitable material, e.g. a resilientthermoplastic. Preferred materials include reticulated filtrationpolyurethane foams with small apertures or pores.

In FIG. 14, the outlet pipe (347) communicates with a layer of foam(364) formed of a suitable material, e.g. a resilient thermoplastic.Again, preferred materials include reticulated filtration polyurethanefoams with small apertures or pores.

In all of FIGS. 13, 14 and 15, in use, the pipe (346) ends in one ormore openings that deliver the irrigant fluid directly from the woundbed over an extended area.

Similarly, the outlet pipe (347) effectively collects the fluid radiallyfrom the wound periphery when the dressing is in use.

Referring to FIGS. 16A and 16B, the dressing is also provided with awound filler (348) under a circular backing layer (342).

This also comprises a generally toroidal conformable hollow body,defined by a membrane (349) which is filled with a fluid, here air ornitrogen, that urges it to the wound shape.

The filler (348) may be permanently attached to the backing layer (342)via a first boss (351) and a layer of foam (364) formed of a suitablematerial, e.g. a resilient thermoplastic. Again, preferred materialsinclude reticulated filtration polyurethane foams with small aperturesor pores.

The first boss (351) and foam layer (364) are respectively heat-sealedto the backing layer (342) and the boss (351).

An inflation inlet pipe (350), inlet pipe (346) and outlet pipe (347)are mounted centrally in the first boss (351) in the backing layer (342)above the toroidal hollow body (348).

The inflation inlet pipe (350), inlet pipe (346) and outlet pipe (347)respectively each extend in a pipe (353), (354) and (355) through acentral tunnel (356) in the hollow body (348) to a second boss (357)attached to the toroidal hollow body (348).

The pipe (353) communicates with the interior of the hollow body (348),to permit inflation of the body (348). The pipe (354) extends radiallythrough the second boss (357) to communicate with an inlet manifold(352), formed by a membrane (361) that is permanently attached to thefiller (348) by heat-sealing in the form of a reticulated honeycomb withopenings (362) that deliver the irrigant fluid directly to the wound bedover an extended area. The pipe (355) collects the fluid flowingradially from the wound centre when the dressing is in use.

This form of the dressing is a more suitable layout for deeper wounds

In FIG. 17, the dressing is similar to that of FIG. 16, except that thetoroidal conformable hollow body, defined by a membrane (349), is filledwith a fluid, here a solid particulates, such as plastics crumbs orbeads, rather than a gas, such as air or an inert gas, such as nitrogenor argon, and the inflation inlet pipe (350) and pipe (353) are omittedfrom the central tunnel (356).

Examples of contents for the body (348) also include gels, such assilicone gels or preferably cellulosic gels, for example hydrophiliccross-linked cellulosic gels, such as Intrasite™ cross-linked materials.Examples also include aerosol foams, and set aerosol foams, e.g.CaviCarer™ foam.

Referring to FIGS. 18A, 18B, and 19, another form for deeper wounds isshown. This comprises a circular backing layer (342) and a chamber (363)in the form of a deeply indented disc much like a multiple Maltese crossor a stylised rose.

This is defined by an upper impervious membrane (361) and a lower porousfilm (362) with apertures (364) that deliver the irrigant fluid directlyfrom the wound bed over an extended area. A number of configurations ofthe chamber (363) are shown, all of which are able to conform well tothe wound bed by the arms closing in and possibly overlapping ininsertion into the wound.

In a particular design of the chamber (363), shown lowermost, on of thearms extended and provided with an inlet port at the end of the extendedarm. This provides the opportunity for coupling and decoupling theirrigant supply remote from the dressing and the wound in use.

An inlet pipe (346) and outlet pipe (347) are mounted centrally in aboss (351) in the backing layer (342) above the chamber (363). The inletpipe (346) is permanently attached to, and communicate with the interiorof, the chamber (363), which thus effectively forms an inlet manifold.The space above the chamber (363) is filled with a loose gauze packing(364).

In FIG. 18, the outlet pipe (347) collects the fluid from the interiorof the dressing from just under the wound-facing face (343) of thebacking layer (342).

A variant of the dressing of FIG. 18 is shown in FIG. 19. The outletpipe (347) is mounted to open at the lowest point of the space above thechamber (363) into a piece of foam (374).

In FIG. 20, the dressing is similar to that of FIG. 13, except that theinlet pipe (352) communicates with an inlet manifold (353), formed by amembrane (361) with apertures (362), over the upper surface of thegenerally downwardly domed wound hollow filler (348), rather thanthrough it.

In FIG. 22, the dressing is similar to that of FIG. 14, with theaddition of an inlet manifold (353), formed by a membrane (361) withapertures (362), over the lower surface of the generally downwardlydomed annular wound hollow filler.

In FIG. 21, the generally downwardly domed annular wound hollow filleris omitted.

Referring to FIG. 23, another form for deeper wounds is shown. An inletpipe (346) and outlet pipe (347) are mounted centrally in a boss (351)in the backing layer (342) above a sealed-off foam filler (348). Theinlet pipe (346) is permanently attached to and passes through thefiller (348) to the wound bed. The outlet pipe (347) is attached to andcommunicates with the interior of, a chamber (363) defined by a porousfoam attached to the upper periphery of the filler (348). The chamber(363) thus effectively forms an outlet manifold.

In FIG. 24, the foam filler (348) is only partially sealed-off. Theinlet pipe (346) is permanently attached to and passes through thefiller (348) to the wound bed. The outlet pipe (347) is attached to andcommunicates with the interior of the foam of the filler (348). Fluidpasses into an annular gap (349) near the upper periphery of the filler(348) into the foam, which thus effectively forms an outlet manifold.

FIGS. 25 and 26 show dressings in which the inlet pipe (346) and outletpipe (347) pass through the backing layer (342).

In FIG. 25, they communicates with the interior of a porous bag filler(348) defined by a porous film (369) and filled with elasticallyresilient plastics bead or crumb.

In FIG. 26, they communicate with the wound space just below a foamfiller (348). The foam (348) may CaviCare™ foam, injected and formed insitu around the pipes (346) and (347).

Referring to FIG. 27, the apparatus (1) for aspirating, irrigatingand/or cleansing wounds is a major a variant of the apparatus shown inFIG. 1.

The device for moving fluid through the wound and means for fluidcleansing (17) in FIG. 1 is a peristaltic pump (18), e.g. preferably asmall portable peristaltic pump, acting on the fluid circulation tube(13) downstream of the dressing (2) to apply a low negative pressure onthe wound.

In the apparatus (1) shown in FIG. 27, the peristaltic pump (18) isreplaced by:

-   -   a) a peristaltic pump, acting on the fluid supply tube (7)        upstream of the dressing (2), and    -   b) a vacuum pump assembly with pressure regulating means, acting        on the fluid circulation tube (13) downstream of the dressing        (2),        to apply a low negative pressure on the wound.

The vacuum pump assembly comprises a tank (911) with

-   -   an inlet tube (912) connecting to the fluid circulation tube        (13) and communicating with the upper part of the tank (911),    -   a waste tube (913) connecting to a waste pump (914) with waste        bag (915) and communicating with the lower part of the tank        (911),    -   a pump tube (916) connecting to a vacuum pump (918) and        communicating with the upper part of the tank (911), and    -   an outlet tube (917) connecting to the fluid circulation tube        (13) to the means for cleansing (17) and communicating with the        lower part of the tank (911).

The vacuum pump (918) is controlled by a pressure feedback regulator(919) through an electrical line (920), the regulator receiving signalsfrom a tank sensor (921) in the upper part of the tank (911), and adressing sensor (922) in the wound space respectively via lines (923)and (924).

The operation of the apparatus (1) is similar to that of the apparatusin FIG. 1 mutatis mutandis.

The pressure feedback regulator (919) regulates the pressure at thewound and/or the tank (911).

If the amount of fluid in circulation becomes excessive, e.g. becausethe wound continues to exude heavily, the waste pump (914) may bestarted to transfer fluid from the lower part of the tank (911) to thewaste bag (915).

The use of the apparatus of the present invention will now be describedby way of example only in the following Examples:

Example 1—Microfiltration Removal of Bioburden, IncludingMicro-Organisms from a Single-Phase System

A single phase circuit essentially as in FIG. 1, but with a sample portS1 between the wound dressing and the pump and a sample port S2downstream of a sterile 0.22 .mu.m filter filtration device as thecleansing means was sterilised by γ-irradiation

Prior to inoculation with the test organism (S aureus NCTC 10788), thewound reservoir was filled with 45 ml sterile MRD (maximum recoverydiluent) and then the MRD was inoculated with the test organism to givea final concentration of 10⁴ cfu/ml.

The culture was allowed to pre-circulate around the circuit (bypassingthe sterile 0.22 μm filter) prior to being circulated through thefiltration device. A sample (0.5 ml) of the pre-circulation fluid wastaken from port S1 at 30 and 60 minutes. This was serially diluted inMRD to 10⁻³ and duplicate 1 ml tryptone soya agar (TSA) plates wererepared from each dilution according to a standard validated protocol.Plates were incubated for at least 72 hours at 32° C. prior to counting.

After 1 hour, the fluid was allowed to circulate through the filtrationdevice. 0.5 ml samples of the circulating fluid were taken from ports S1at T=10, 30, 50 and 70 minutes and S2 at T=0, 20, 40, 60 and 80 minutes.All samples were enumerated as described above.

Results

TABLE 1 Bacterial counts of pre-circulation fluid taken from the singlephase system Sample time (minutes) Mean count (cfu/ml) Log₁₀ count(cfu/ml) 30 2.31 × 10⁴ 4.36 60 1.87 × 10⁴ 4.27

TABLE 2 Bacterial counts of post-wound reservoir (port S1) fluid takenfrom the single phase Exudialysis system Sample time (minutes) Meancount (cfu/ml) Log₁₀ count (cfu/ml) 10 6.30 × 10³ 3.80 30 4.10 × 10³3.61 50 1.77 × 10³ 3.25 70 1.23 × 10³ 3.09

TABLE 3 Bacterial counts of post-filtration (port S2) fluid taken fromthe single phase Exudialysis system Sample time (minutes) Mean count(cfu/ml) Log₁₀ count (cfu/ml) 0 <1.0 × 10¹ <1.00 20 <1.0 × 10¹ <1.00 40<1.0 × 10¹ <1.00 60  1.0 × 10¹ 1.00 80 <1.0 × 10¹ <1.00

Conclusions

The single phase system was able to immediately remove bacterial cellsfrom the wound circuit after passing through 0.22 .mu.m filter byapproximately 3 logs and cause a gradual reduction in the overallnumbers of circulating bacteria.

Example 2—Inhibition of Elastase in a Two-Phase System (Static SecondPhase)

a) Preparation of an Immobilised Elastase Antagonist—a Conjugate (‘theInhibitor’) of 4-(2-aminoethyl)-benzenesulfonyl fluoride (AEBSF) withpoly(maleic anhydride-alt-methylvinylether), and with 1%5-(2-aminoethylamino)-1-naphthalenesulfonic acid (EDANS) Fluorescent Tag

To a magnetically stirred solution of MAMVE (1.646 g, 10.5 mmol units)in DMF (100 ml) was added EDANS (30.4 mg, 0.1 mmol) in DMF (2 ml). After15 minutes, a solution of AEBSF hydrochloride (2.502 g, 10.4 mmol) andtriethylamine (1.056 g, 10.4 mmol) in DMF (20 ml) was added dropwise.After 5 h, this solution was precipitated dropwise into 0.5 M HCl (2000ml), Buchner filtered and washed with 0.5 M HCl. The product was vacuumdesiccated to dryness and stored at −4° C. Yield 3.702 g, 98%.

To a magnetically stirred solution of MAMVE (2.000 g, 12.8 mmol units)in DMF (100 ml) was added EDANS (37.0 mg, 0.1 mmol) in DMF (2 ml). After15 minutes, a solution of phenethylamine (1.537 g, 12.7 mmol) in DMF (10ml) was added dropwise. After 5 h, this solution was precipitateddropwise into 0.5 M HCl (2000 ml), Buchner filtered and washed with 0.5M HCl. The product was vacuum desiccated to dryness and stored at roomtemperature.

Yield 3.426 g, 97%.

b) Elastase Inhibition

A two-phase circuit essentially as in FIG. 1 was used, with a two-phasecleansing means with static second phase, but with a sample portdownstream of a cleansing means.

The cleansing means is a MiCroKros Cross Flow Syringe Filter (SpectrumLabs Inc) PS/400K MWCO 8 cm², with two separate chambers, any fluid inthe outer being held static.

The outer chamber was filled with 2 mg/ml Inhibitor solution (˜1 ml inTRIS) and connected up to the tubing. The inlet and outlet tubing wasplaced in a TRIS solution and TRIS was flushed through the inner chamberof the MiCoKros syringe and the tubing for 5 mins. The tubing was thenemptied. 2 ml of elastase (0.311 mg/ml) was pipetted into the woundcircuit.

The tubes were placed in the reservoir and the pump and the timer werestarted simultaneously.

10 microlitre samples were taken every hour from the wound circuit forsix hours and assayed in the following way immediately after sampling. Acontrol of static elastase was assayed at every time point in order todetermine the decrease in activity over the 6 hours.

c) Elastase Activity Assay

The elastase substrate N-Succ-(Ala)₃-nitronilide was prepared (10 mg/mlin DMSO). 25 microlitre of the N-Succ-(Ala)₃-nitronilide (10 mg/ml) wasadded to 2.475 ml of TRIS in a 4.5 ml capacity disposable cuvette. Thismixing was completed 10 mins before the elastase solution was due to beadded into the cuvettes (in order to ensure the substrate was mixedwell). The 10 microlitre sample was then added to each cuvette and mixedwell. The sample was incubated at room temp for 40 mins and theabsorbance at 405 nm recorded.

Results and Conclusions

TABLE 1 The absorbance detected after 40 mins incubation (405 nm) forelastase + TRIS. The experiment was repeated in triplicate and controlof static elastase was recorded every hour. TRIS Time/h Run 1 Run 2 Run3 Elastase control 0 0.266 0.284 1 0.255 0.258 0.239 0.283 2 0.271 0.2420.225 0.284 3 0.219 0.218 0.209 0.291 4 0.208 0.203 0.203 0.277 5 0.1970.17 0.194 0.304 6 0.198 0.161 0.182 0.288 elastase 0.267 0.289 0.281final

TABLE 2 The absorbance detected after 40 mins incubation (405 nm) forelastase + MAMVE-AEBSF. The experiment was repeated in triplicate andcontrol of static elastase was recorded every hour. The average of allthe elastase control experiments was used to calculate the 100% activityfor 0 h. MAMVE-AEBSF Time/h Run 1 Run 2 Run 3 Elastase control 0 0.3620.39 0.371 1 0.234 0.308 0.267 0.4 2 0.158 0.215 0.193 0.374 3 0.0810.161 0.128 0.363 4 0.064 0.12 0.083 0.366 5 0.046 0.073 0.048 0.375 60.025 0.061 0.034 0.348

The average of all the elastase control experiments was used tocalculate the 100% activity for 0 h.

TABLE 3 The average % elastase activity for 3 variables, with the SD %Average SD Time/h TRIS AEBSF Time/h TRIS AEBSF 0 100.00 100.00 0 1 88.5572.47 1 3.61 9.96 2 86.90 50.70 2 8.22 7.73 3 76.07 33.14 3 1.95 10.80 472.30 23.92 4 1.02 7.65 5 66.06 14.96 5 5.23 4.04 6 63.70 10.75 6 6.555.03

The results indicate that for the elastase+Tris solution there is a60-70% drop in activity. This can be explained as a dilution effect asthe 2 ml of elastase mix with the 1 ml TRIS in the outer chamber (⅔).This indicates that the system is inert to elastase and the completemixing/diffusion across the membrane occurs within 3 h.

The elastase+MAMVE-AEBSF within the 6 h shows a 90% drop in elastaseactivity.

Example 3—Sequestration of Iron Ions from a Two-Phase System (StaticSecond Phase)

A two-phase circuit essentially as in FIG. 1 was used, with a two-phasecleansing means with static second phase, but with a sample portdownstream of a cleansing means, the latter being a Slide-A-Lyzerdialysis cassette (Pierce, 10,000 MWCO, 3-15 ml capacity, Product#66410) in a chamber of a Slide-A-Lyzer.

The cassette was loaded with one of the following:

-   -   a) 5 ml of phosphate buffer saline (PBS),    -   b) starch control (40, 120 and 200 mg/ml) or    -   c) starch-desferrioxamine (DFO) conjugate (supplied by        Biomedical Frontiers Inc.) in solution (40, 120 and 200 mg/ml).

Each dialysis cassette was placed in a Slide-A-Lyzer chamber. In thisarrangement, the cassette load is separated from the recirculating firstfluid by the 10,000 MWCO membrane referred to above.

Transferrin (10 mg/ml, 35 ml volume) was injected into the sample portand circulated around the flow system by a Masterflex pump (Model No.7523-37) at different flow rates (0.54, 0.82, 1.08 and 1.35 ml/min) for8 hours.

Samples were collected at 0, 2, 4, 6 and 8 hours.

The iron content of the samples was measured using a ferrozine assay asfollows: The sample was mixed with 50 mM acetate buffer, pH 4.8 toliberate iron from transferrin. Ascorbate (30 mM) was added to thesample to reduce released Fe (III) ions to Fe (II) ions. Ferrozine (5mM) was mixed with the sample forming a coloured complex with Fe (II)ion. The absorbance was measured using UNICAM UV4-100 UV-Visspectrophotometer V3.32 (serial no. 022405).

Results and Conclusions

Starch-DFO picked up iron from transferrin in a dose dependent mannerover 8 hours. Approximately 20-25% iron removal occurred in the presenceof 200 mg/ml of starch-DFO after 8 hours recirculation.

In the presence of different concentrations of starch control or PBS theiron content of transferrin dropped slightly due to a dilution effectbut then slowly returned to normal, suggesting that iron pick-up bystarch-DFO was mediated by DFO alone.

The iron pick-up profile for transferrin was similar at different flowrates suggesting that flow had no effect on iron transfer across thedialysis membrane.

Example 4—Infusion of Antibiotic from the Second Phase of a Two-PhaseSystem (Moving Second Phase)

A two-phase circulation system essentially as in FIG. 1 with the second(dialysate) circuit essentially as in FIG. 2 was used. The pumps wereperistaltic acting on silicone tubing. The second circuit was providedwith a reservoir of dialysate with which to modify the wound fluid (50ml Falcon centrifuge tube). The wound circuit was connected into theends of a luer-fitting hollow fibre tangential membrane dialysis unit(Spectrum® MicroKros® X14S-100-04N, 8 cm2 surface area, 400 KD Mol. Wt.cut off). The dialysate circuit was connected to the side ports of thesame dialysis unit so that flow between the wound circuit and thedialysate circuit were in a counter current direction.

The wound circuit was flushed first with ethanol and then with sterilewater as per the manufacturers' instruction. The wound reservoir wasfilled with 20 ml of sterile water. The wound pump was run at a speedsetting of 100, which generated a measured flow rate of 2.09 ml⁻¹ in thewound circuit. The dialysate circuit was flushed first with ethanol andthen with sterile water as per the manufacturers instruction. Thedialysate reservoir was filled with 20 ml of sterile water. Thedialysate pump was run at a speed setting of 100, which generated ameasured flow rate of 1.93 ml min⁻¹ in the dialysate circuit. Samples (1ml) were removed from the wound and the dialysate reservoirs by means ofa length of silicone tube with a luer fitting attached to a 2 ml syringe

At the start of the experiment, 5 ml of sterile water was removed fromthe dialysate reservoir and 5 ml of a 5 mg ml⁻¹ solution of gentamycinsulphate was added (EP standard gentamycin sulphate, CRS; (activity 616IU mg⁻¹)). Both the wound and the dialysate pumps were started at thesame time. Samples were removed from the dialysate circuit and the woundcircuit at intervals over 230 minutes. No volumes were replaced duringthe experiment.

Samples (1 ml) were diluted with 2 ml of sterile water and the UVabsorbance at 190 nm was checked to get an approximate measure of themovement of gentamycin from the dialysate circuit to the wound circuitusing a previously generated standard curve.

Samples were subsequently analysed with a quantitative zone ofinhibition assay for gentamycin activity according to an assay that usesStaphylococcus epidermidis as the indicator bacteria.

Results and Conclusions

The results of the antimicrobial activity-zone of inhibition assays ofthe fluid show that the level of gentamycin in the wound circuitincreases steadily over 230 min with the rate of increase slowing as thelevels of drug in the two circuits approach each other. The gentamycinlevels in the dialysate circuit show a steady decrease as expected ifdrug is moving from the dialysate circuit to the wound circuit. At thepressure and flow rates useful in clinical practice, drugs for woundhealing can be delivered in acceptable quantities and on an acceptabletimescale.

Example 5—Regeneration of Glutathione (Reduction of Oxidised Glutathione(GSSG) to Glutathione (GSH) by Localised Glutathione Reductase (GR) andCofactor NADP (Reduced Form) in a Two-Phase System (Static Second Phase)

A two-phase circuit essentially as in FIG. 1 was used, with a two-phasecleansing means with static second phase, but with a sample portdownstream of a cleansing means, the latter being a Slide-A-Lyzerdialysis cassette (Pierce, 10,000 MWCO, 3-15 ml capacity, Product#66410) in a chamber of a Slide-A-Lyzer.

Into the internal cavity of separate 15 ml capacity Slide-A-Lyzercassettes was injected 5 ml of each stock solution:

-   -   a) 2 mg/ml NADP prepared in distilled water (NADP)    -   b) 2 mg/ml Glutathione reductase prepared in NADP stock solution        (GR+NADP)    -   c) 2 mg/ml Glutathione reductase prepared in distilled water        (GR) in triplicate.

The cassettes were laid flat and into the upper, outer cavity wasaliquoted 15 ml of GSSG stock solution (50 microM GSSG prepared indistilled water (30.6 mg/l). This was circulated around the first phasecircuit. The latter was sampled (1 ml) every hour for 6 h in total into1.5 ml capacity disposable UV cuvettes. At the end of this period, eachaliquot was assayed using a Glutathione Assay Kit (from Calbiochem).Triplicates were averaged and SD determined for each data point. Thesedata were plotted as GSSG concentration versus time for each of thethree control systems.

Results & Conclusions

GSSG was depleted by the combination of GR and its cofactor NADP to asignificantly greater extent than by GR or NADP alone. Thus depletion isnot attributable to non-specific binding. Approximately 40% of GSSG wasdepleted in 6 h at the stated enzyme and cofactor concentrations.

Example 6—Degradative Removal of Bacterial Autoinducers from aSingle-Phase System

The exchange of extra cellular signalling molecules called auto-inducersis used by bacteria and is essential to the co-ordinatation of theexpression of key bacterial virulence genes activated at a criticalbacterial cell density, and thus to achieving successful bacterialcolonization and invasion of tissue. The system is called QuorumSensing. Conversely, (usually enzymic) degradation or sequestration ofthe autoinducer species is one way to disrupt the essentialcommunication and aid the prevention of infection in wounds.

The AiiA enzyme is a degrader of the 3-oxododecylhomoserine lactonesignal molecule which is used by S. aureus as an autoinducer.

The AiiA enzyme used is one produced at the University of Nottingham andis bound to a maltose binding protein.

a) Preparation of AiiA Enzyme Bound to a Polymer Support

Cyanogen bromide activated Sepharose 6 MB (from Sigma) (200-300 μmdiameter for a higher through-flow rate) were washed in 1 mMhydrochloric acid and allowed to soak and swell for a period of 30minutes. The gel was washed with multiple volumes of distilled water andthen with NaHCO₃/NaCl pH 8.5 and used immediately.

The AiiA enzyme solution (approx. 1 mg/ml) was added to the polymersupport beads and allowed to stand at 4° C. overnight. The coupled beadswere washed with pH 8.5 NaHCO₃/NaCl and stored as a slurry. The washingsfrom the beads were also collected in order to determine the amount ofuncoupled enzyme and hence the coupling efficiency.

Blank, uncoupled beads were used as a control.

Different amounts of the enzyme coupled beads, 1 mg, 10 mg and 100 mg,are trapped in a chamber defined by two glass frits across a cylindricalglass cylinder with axial inlet and outlet ports for throughflow, whichformed the cleansing means in a single phase system, which also has asample port downstream of a cleansing means. A 10 microM stock of3-oxododecylhomoserine lactone (ODHSL) is pumped through the chamber at1.93 ml min⁻¹ and 37° C. for 6 hr.

The circulating fluid is sampled (1 ml) every hour for 6 h in total into1.5 ml capacity disposable UV cuvettes.

At the end of this period, each aliquot was assayed using the assay ofSwift et al. 1997, J. Bacteriol. 179: 5271-5281, which usesbioluminescence-based plasmid reporter systems in E. coli. The 100 mgsample shows an 86% reduction in ODHSL concentration in 6 hours.

1.-10. (canceled)
 11. An altered pressure device for treating a wound,the device comprising: a cover sized to fit over the wound and includingan opening therein, the cover defining an encapsulated space surroundingthe wound; an intermediate material layer positionable in theencapsulated space; an altered pressure source communicating with theencapsulated space via a length of tubing coupled with the source, thetubing having a proximal end; and a proximal end piece connected to theproximal end of the tubing and including a flange at a lower portionthereof, wherein the flange is comprised of a substantially planarsurface adapted to be engageable with the periphery of the opening inthe cover to create a seal.
 12. The altered pressure device of claim 11,wherein the proximal end piece is attachable to the cover adjacent theopening.
 13. The altered pressure device of claim 12, further comprisinga semi-solid insertable within the encapsulated space.
 14. The alteredpressure device of claim 12, wherein the tubing communicating thealtered pressure source with the encapsulated space is flush with theflange.
 15. The altered pressure device of claim 11, further comprisinga semi-solid insertable within the encapsulated space.
 16. The alteredpressure device of claim 11, wherein the tubing communicating thealtered pressure source with the encapsulated space is flush with theflange.
 17. A device for treating a wound with non-atmospheric pressure,the device comprising: a backing layer configured to form a closure overa wound, the backing layer including an opening therein; a fillermaterial positionable in an enclosed space between the backing layer andthe wound; a positive or negative pressure source configured to applypositive or negative pressure to the wound through a conduit in fluidcommunication with the positive or negative pressure source, the conduithaving a proximal end; and a boss connected the conduit, wherein theboss comprises a substantially planar surface configured to engage witha periphery of the opening in the backing layer to create a seal. 18.The device of claim 17, wherein the boss includes a flange at a lowerportion thereof, wherein the flange comprises the substantially planarsurface configured to engage with the periphery of the opening in thebacking layer.
 19. The device of claim 18, wherein the proximal end ofthe conduit is connected to the boss.
 20. The device of claim 19,further comprising a gel positionable within the enclosed space betweenthe backing layer and the wound.
 21. The device of claim 19, wherein theconduit extends parallel with the substantially planar surface of theboss at the connection of the conduit with the boss.
 22. The device ofclaim 17, wherein the proximal end of the conduit is connected to theboss.
 23. The device of claim 17, further comprising a gel positionablewithin the enclosed space between the backing layer and the wound. 24.The device of claim 17, wherein the conduit extends parallel with thesubstantially planar surface of the boss at the connection of theconduit with the boss.
 25. The device of claim 17, wherein the positiveor negative pressure source comprises a pump.
 26. The device of claim25, wherein the pump is a negative pressure pump, and the conduit is anoutflow pipe.
 27. The device of claim 17, wherein the conduit is mountedin the boss above the filler material.
 28. The device of claim 17,wherein the boss is heat-sealed to the backing layer.